The neurochemistry of human aggression.

Various data from scientific research studies conducted over the past three decades suggest that central neurotransmitters play a key role in the modulation of aggression in all mammalian species, including humans. Specific neurotransmitter systems involved in mammalian aggression include serotonin, dopamine, norepinephrine, GABA, and neuropeptides such as vasopressin and oxytocin. Neurotransmitters not only help to execute basic behavioral components but also serve to modulate these preexisting behavioral states by amplifying or reducing their effects.

Manipulation of nicotinic acetylcholine receptors differentially affects behavioral inhibition in human subjects with and without disordered baseline impulsivity.

Rationale: Evidence for a relationship between cigarette smoking and attention-deficit/hyperactivity disorder (ADHD) has prompted investigations into nicotinic treatments for this disorder. Impulsivity is a hallmark of ADHD and is measured in the laboratory as behavioral inhibition (BI) using the stop signal task (SST). Acute nicotine improves SST performance in adolescents and young adults who have both ADHD and impaired baseline SST performance, raising questions about the role of nicotinic acetylcholine receptor function in BI.

Towards a glutamate hypothesis of depression: an emerging frontier of neuropsychopharmacology for mood disorders.

Half a century after the first formulation of the monoamine hypothesis, compelling evidence implies that long-term changes in an array of brain areas and circuits mediating complex cognitive-emotional behaviors represent the biological underpinnings of mood/anxiety disorders. A large number of clinical studies suggest that pathophysiology is associated with dysfunction of the predominant glutamatergic system, malfunction in the mechanisms regulating clearance and metabolism of glutamate, and cytoarchitectural/morphological maladaptive changes in a number of brain areas mediating cognitive-emotional behaviors. Concurrently, a wealth of data from animal models have shown that different types of environmental stress enhance glutamate release/transmission in limbic/cortical areas and exert powerful structural effects, inducing dendritic remodeling, reduction of synapses and possibly volumetric reductions resembling those observed in depressed patients.

Functional brain imaging of nicotinic effects on higher cognitive processes.

Significant advances in human functional brain imaging offer new opportunities for direct observation of the effects of nicotine, novel nicotinic agonists and nicotinic antagonists on human cognitive and behavioral performance. Careful research over the last decade has enabled investigators to explore the role of nicotinic systems on the functional neuroanatomy and neural circuitry of cognitive tasks in domains such as selective attention, working memory, episodic memory, cognitive control, and emotional processing. In addition, recent progress in understanding functional connectivity between brain regions utilized during cognitive and emotional processes offers new opportunities for examining drug effects on network-related activity.

The cholinergic hypothesis of cognitive aging revisited again: cholinergic functional compensation.

It is now possible to reevaluate the cholinergic hypothesis of age-related cognitive dysfunction based on a synthesis of new evidence from cholinergic stimulation studies and cognitive models. We propose that a change of functional circuitry that can be observed through a combination of pharmacologic challenge and functional neuroimaging is associated with age-related changes in cholinergic system functioning. Psychopharmacological manipulations using cholinergic agonists and antagonists have been consistent in replicating patterns of aging seen in functional imaging studies.

Plasma homovanillic acid correlates inversely with history of childhood trauma in personality disordered and healthy control adults.

Studies of the cerebrospinal fluid (CSF) level of the dopamine metabolite, homovanillic acid (HVA), suggest a relationship between CSF HVA concentration and history of childhood trauma. In this study, the authors test the hypothesis that this relationship is also present using peripheral levels of HVA in healthy volunteers and in personality disordered subjects. 68 personality disordered (PD) and healthy control (HC) subjects were chosen, in whom morning basal plasma HVA (pHVA) concentrations and an assessment of childhood trauma were obtained.

Increased memory load-related frontal activation after estradiol treatment in postmenopausal women.

Prior research shows that menopause is associated with changes in cognition in some older women. However, how estrogen loss and subsequent estrogen treatment affects cognition and particularly the underlying brain processes responsible for any cognitive changes is less well understood. We examined the ability of estradiol to modulate the manipulation of information in working memory and related brain activation in postmenopausal women.

Kafka, paranoic doubles and the brain: hypnagogic vs. hyper-reflexive models of disrupted self in neuropsychiatric disorders and anomalous conscious states.

Kafka's writings are frequently interpreted as representing the historical period of modernism in which he was writing. Little attention has been paid, however, to the possibility that his writings may reflect neural mechanisms in the processing of self during hypnagogic (i.e.

Klaus Conrad (1905-1961): delusional mood, psychosis, and beginning schizophrenia.

Klaus Conrad's major contribution to the phenomenology of psychosis focused on the patient's experiences during the prodromal and early psychotic phases of schizophrenia. The literature in English concerning his work is sparse, in part because Conrad's work contains complex concepts that lose much in translation. This communication attempts to clarify Conrad's thought, especially as it pertains to the role of mood and delusions in beginning psychosis and its underlying neurobiology.

A critical review of human endotoxin administration as an experimental paradigm of depression.

The syndrome called depression may represent the common final pathway at which different aetiopathogenic processes converge. One such aetiopathogenic process is innate immune system activation. Some depressed patients have increased levels of inflammatory cytokines and other immunologic abnormalities.

Effects of acute ultra-low dose mecamylamine on cognition in adult attention-deficit/hyperactivity disorder (ADHD).

Objective: Nicotinic cholinergic stimulation has known beneficial effects in attention-deficit/hyperactivity disorder (ADHD). Mecamylamine is a non-competitive nicotinic antagonist which is reported in several animal studies to have paradoxical positive effects on cognition at ultra-low doses. Comparable studies in humans have not been conducted.

Ichi, Ni, 3, 4: neural representation of kana, kanji, and Arabic numbers in native Japanese speakers.

The Japanese language represents numbers in kana digit words (a syllabic notation), kanji numbers and Arabic numbers (logographic notations). Kanji and Arabic numbers have previously shown similar patterns of numerical processing, and because of their shared logographic properties may exhibit similar brain areas of numerical representation. Kana digit words require a larger phonetic component, and therefore may show different areas of numerical representation as compared to kanji or Arabic numbers.

Adult age differences in the access and deletion functions of inhibition.

This study examined age differences in working memory using a delayed-matching-to-sample (DMTS) task. Based on the inhibitory decline hypothesis, which posits that older adults are more susceptible to interference, age differences were expected to be greater for older adults when irrelevant information was present during encoding. Two experiments tested both the access and deletion functions of inhibition.

Riluzole in the treatment of mood and anxiety disorders.

Recent advances implicate amino acid neurotransmission in the pathophysiology and treatment of mood and anxiety disorders. Riluzole, which is approved and marketed for the treatment of amyotrophic lateral sclerosis, is thought to be neuroprotective through its modulation of glutamatergic neurotransmission. Riluzole has multiple molecular actions in vitro; the two that have been documented to occur at physiologically realistic drug concentrations and are therefore most likely to be clinically relevant are inhibition of certain voltage-gated sodium channels, which can lead to reduced neurotransmitter release, and enhanced astrocytic uptake of extracellular glutamate.

Nicotinic versus muscarinic blockade alters verbal working memory-related brain activity in older women.

Objectives: An important aspect of furthering our understanding of the central nervous system function after menopause is to examine the cerebral circuitry that appears to be influenced by cholinergic antagonist drugs in the presence and absence of estrogen. This pilot study investigated the effects of two anticholinergic drugs on brain activation and working memory performance in postmenopausal women not taking estrogen. This approach simulates the effects of age- or disease-related neuroreceptor or neuronal loss by temporarily blocking pre- and postsynaptic muscarinic and nicotinic cholinergic receptors.

Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder.

Objective: The strong association between ADHD and cigarette smoking and the known effects of nicotine on cognition has lead to interest in the role of cholinergic function in ADHD cognitive deficits. We have previously demonstrated that acute nicotine improves behavioral inhibition in adolescents with ADHD. This study examined acute nicotine in young adults with ADHD-Combined type on cognitive domains including behavioral inhibition, delay aversion, and recognition memory.

Estradiol interacts with the cholinergic system to affect verbal memory in postmenopausal women: evidence for the critical period hypothesis.

Estradiol has been shown to interact with the cholinergic system to affect cognition in postmenopausal women. This study further investigated the interaction of estradiol and cholinergic system functioning on verbal memory and attention in two groups of healthy younger (ages 50-62) and older (ages 70-81) postmenopausal women. Twenty-two postmenopausal women were randomly and blindly placed on 1 mg of 17-beta estradiol orally for 1 month then 2 mg for 2 months or matching placebo pills after which they participated in three anticholinergic challenge sessions when verbal memory and attention were assessed.

Missing links in phenomenological clinical neuroscience: why we still are not there yet.

Purpose Of Review: The phenomenology or systematic study of the patient's subjective experience in neuropsychiatric disorders is widely recognized as important. The methods used, the type of 'knowledge' obtained and the relationship of these observations to standard methods of clinical neuroscience, however, remain ill-defined and highly controversial.

Recent Findings: Advances in the phenomenology of consciousness, self, body-experience, time-perception and intersubjectivity of neuropsychiatric disorders have been made.

Estrogen administration negatively alters mood following monoaminergic depletion and psychosocial stress in postmenopausal women.

Differences in the rates of affective disorders between women and men may relate to gender differences in gonadal steroid levels such as estrogen that have effects on brain monoamines important to mood regulation. Changes in estrogen secretion patterns during the perimenopause and menopause may be relevant to the increased risk for affective symptoms at that time. This study examined whether 17beta-estradiol (E2) administration can modify the mood effects of experimental psychosocial stress following acute monoamine depletion in postmenopausal women.

Sex differences in visual-spatial learning using a virtual water maze in pre-pubertal children.

Gonadal steroid effects during puberty are often hypothesized to account for the male advantage seen in certain spatial tasks. One spatial task where males consistently show better performance than females is the Morris Water Task in which subjects must navigate to a goal location in a pool. We examined whether sex differences exist in pre-pubertal children completing a Virtual Morris Water Task, which has previously shown strong sex differences in adults.

Central nicotinic cholinergic systems: a role in the cognitive dysfunction in attention-deficit/hyperactivity disorder?

Theories of the neurobiological basis of Attention-Deficit/Hyperactivity Disorder (ADHD) have largely focused on dysregulation of central dopaminergic function. However, other neurotransmitter systems may be implicated in specific cognitive deficits in ADHD. Interest in the potential involvement of nicotinic cholinergic systems in ADHD has arisen in part from the observation that adolescents and adults with ADHD smoke cigarettes at significantly higher rates than people without this disorder.

Increased 5-HT(2A) receptor binding in euthymic, medication-free patients recovered from depression: a positron emission study with [(11)C]MDL 100,907.

Objective: A previous positron emission tomography (PET) study reported increased serotonin 5-HT(2A) receptor binding in unmedicated depressed patients with high scores on the Dysfunctional Attitudes Scale. The purpose of the present study was to use the highly selective 5-HT(2A) receptor ligand [(11)C]MDL 100,907 in a PET imaging paradigm to assess 1) 5-HT(2A) receptor binding potential in euthymic subjects with a history of recurrent depression and 2) the relationship between receptor binding and scores on the Dysfunctional Attitudes Scale.

Method: Cortical 5-HT(2A) receptor binding was measured in 20 unmedicated, fully recovered unipolar depressed patients and 20 age- and gender-matched comparison subjects.