Depressed mood induction in early cigarette withdrawal is unaffected by acute monoamine precursor supplementation.

BACKGROUND: Cigarette smoking is the leading preventable cause of death; however, quitting is difficult and early relapse is common. Dysphoric mood during early cigarette withdrawal is associated with relapse, and with the exception of bupropion and nortriptyline, few interventions have been developed to prevent this. During early cigarette withdrawal there is an elevation in the levels of monoamine oxidase-A (MAO-A), which removes monoamines excessively and induces oxidative stress and is implicated in creating sad mood. Hence, we conducted a randomized, placebo-controlled, double-blind crossover trial of a dietary supplement designed to counter the effects of elevated MAO-A levels on vulnerability to depressed mood. METHODS: Twenty-one otherwise healthy cigarette smokers completed the protocol, receiving either active dietary supplement followed by washout and placebo or the same in reverse order. The dietary supplement was composed of monoamine precursors (2 g tryptophan, 10 g tyrosine) and blueberry antioxidants (blueberry juice with blueberry extract). Vulnerability to depressed mood was measured by the change in scores of depressed mood on the visual analog scale (VAS) following the sad mood induction paradigm (MIP). RESULTS: There was a significant increase in VAS depressed mood scores after the sad MIP during supplement and placebo, but no difference between active and placebo conditions. There was also a significant increase in urge-to-smoke scores after sad MIP during supplement and placebo but no difference between active and placebo conditions. Reliability of the increase in VAS after MIP was very good. CONCLUSION: The dietary supplement had negligible effect on depressed mood, but sad MIP is a very reliable method that can be applied in future studies to assess other interventions for preventing dysphoric mood during early cigarette withdrawal.

The acute effects of exercise on cortical excitation and psychosocial outcomes in men treated for prostate cancer: a randomized controlled trial.

PURPOSE: Regular exercise improves psychological well-being in men treated for prostate cancer (PCa). For this population and among cancer survivors in general, the effect of a single bout of exercise on self-report or objective measures of psychological well-being has not been examined. We examined the acute effect of a single bout of exercise on the cortical silent period (CSP) and on self-reported mood in men that have received treatment for PCa. METHODS: Thirty-six PCa survivors were randomly assigned to 60 min of low to moderate intensity exercise or to a control condition. Outcomes were assessed immediately before and after either the exercise or the control condition. RESULTS: No significant between-group differences were observed in CSP or mood were observed following the exercise session or control conditions. Participants with higher scores of trait anxiety had significantly shorter CSP at baseline, as well as those receiving androgen deprivation therapy. Age and baseline CSP had a low-moderate, but significant negative correlation. Changes in CSP following the exercise condition were strongly negatively correlated with changes in self-reported vigor. CONCLUSION: While we did not observe any acute effect of exercise on the CSP in this population, the associations between CSP and trait anxiety, age, and vigor are novel findings requiring further examination. IMPLICATIONS FOR CANCER SURVIVORS: Exercise did not acutely affect our participants in measures of psychological well-being. Additional mechanisms to explain the chronic psychosocial benefits of exercise previously observed in men with PCa require further exploration. Clinicaltrials.gov Identifier: NCT01715064 (http://clinicaltrials.gov/show/NCT01715064).

Determining optimal rTMS parameters through changes in cortical inhibition.

OBJECTIVES: Evidence shows that repetitive transcranial magnetic stimulation (rTMS) changes cortical inhibition (CI) and excitability and that these changes may relate to its therapeutic effects. This study aimed to investigate the effects of differing durations or 'doses' of rTMS on cortical inhibition and excitability in healthy subjects. METHODS: Four different experiments were conducted: 1 session of 1200 pulses of 1 or 20 Hz active or sham rTMS; 10 sessions of 1 or 20 Hz active or sham rTMS, 1200 pulses/session; 1 session of 3600 pulses of 1 or 20 Hz active or sham rTMS; 1 session of 6000 pulses of 20 Hz active or sham rTMS. Measures of cortical inhibition and excitability included short-interval intracortical inhibition, long interval cortical inhibition, cortical silent period (CSP), motor evoked potential amplitude, resting motor threshold and intracortical facilitation. RESULTS: Only 6000 pulses of 20 Hz rTMS lead to a significant lengthening of the CSP and therefore potentiation of CI. There were no changes to excitability measures. CONCLUSION: Only high frequency rTMS potentiated CI. Longer treatment durations are required to produce such changes. SIGNIFICANCE: Studies investigating the therapeutic effects of rTMS may benefit from extended dosing with increased number of pulses per session. CSP lengthening may be used to guide treatment response.

Abnormal interhemispheric connectivity in male psychopathic offenders.

BACKGROUND: Psychopathic offenders inevitably violate interpersonal norms and frequently resort to aggressive and criminal behaviour. The affective and cognitive deficits underlying these behaviours have been linked to abnormalities in functional interhemispheric connectivity. However, direct neurophysiological evidence for dysfunctional connectivity in psychopathic offenders is lacking. METHODS: We used transcranial magnetic stimulation combined with electroencephalography to examine interhemispheric connectivity in the dorsolateral and motor cortex in a sample of psychopathic offenders and healthy controls. We also measured intracortical inhibition and facilitation over the left and right motor cortex to investigate the effects of local cortical processes on interhemispheric connectivity. RESULTS: We enrolled 17 psychopathic offenders and 14 controls in our study. Global abnormalities in right to left functional connectivity were observed in psychopathic offenders compared with controls. Furthermore, in contrast to controls, psychopathic offenders showed increased intracortical inhibition in the right, but not the left, hemisphere. LIMITATIONS: The relatively small sample size limited the sensitivity to show that the abnormalities in interhemispheric connectivity were specifically related to the dorsolateral prefrontal cortex in psychopathic offenders. CONCLUSION: To our knowledge, this study provides the first neurophysiological evidence for abnormal interhemispheric connectivity in psychopathic offenders and may further our understanding of the disruptive antisocial behaviour of these offenders.

White matter deficits in psychopathic offenders and correlation with factor structure.

Psychopathic offenders show a persistent pattern of emotional unresponsivity to the often horrendous crimes they perpetrate. Recent studies have related psychopathy to alterations in white matter. Therefore, diffusion tensor imaging followed by tract-based spatial statistics (TBSS) analysis in 11 psychopathic offenders matched to 11 healthy controls was completed. Fractional anisotropy was calculated within each voxel and comparisons were made between groups using a permutation test. Any clusters of white matter voxels different between groups were submitted to probabilistic tractography. Significant differences in fractional anisotropy were found between psychopathic offenders and healthy controls in three main white matter clusters. These three clusters represented two major networks: an amygdalo-prefrontal network, and a striato-thalamo-frontal network. The interpersonal/affective component of the PCL-R correlated with white matter deficits in the orbitofrontal cortex and frontal pole whereas the antisocial component correlated with deficits in the striato-thalamo-frontal network. In addition to replicating earlier work concerning disruption of an amygdala-prefrontal network, we show for the first time that white matter integrity in a striato-thalamo-frontal network is disrupted in psychopathic offenders. The novelty of our findings lies in the two dissociable white matter networks that map directly onto the two major factors of psychopathy.

A meta-analysis of cortical inhibition and excitability using transcranial magnetic stimulation in psychiatric disorders.

OBJECTIVE: To evaluate transcranial magnetic stimulation (TMS) measures of inhibition and excitation in obsessive-compulsive disorder (OCD), major depressive disorder (MDD) and schizophrenia (SCZ). METHODS: Paradigms included: short-interval cortical inhibition (SICI), cortical silent period (CSP), resting motor threshold, intracortical facilitation, and motor evoked potential amplitude. A literature search was performed using PubMed, Ovid Medline, Embase Psychiatry and PsycINFO 1990 through April 2012. RESULTS: A significant Hedge's g was found for decreased SICI (g=0.572, 95% confidence interval [0.179, 0.966], p=0.004), enhanced intracortical facilitation (g=0.446, 95% confidence interval [0.042, 0.849], p=0.030) and decreased CSP (g=-0.466, 95% confidence interval [-0.881, -0.052], p=0.027) within the OCD population. For MDD, significant effect sizes were demonstrated for decreased SICI (g=0.641, 95% confidence interval [0.384, 0.898], p=0.000) and shortened CSP (g=-1.232, 95% confidence interval [-1.530, -0.933], p=0.000). In SCZ, a significant Hedge's g was shown for decreased SICI (g=0.476, 95% confidence interval [0.331, 0.620], p=0.000). CONCLUSION: Inhibitory deficits are a ubiquitous finding across OCD, MDD, SCZ and enhancement of intracortical facilitation is specific to OCD. SIGNIFICANCE: Provides a clear platform from which diagnostic procedures can be developed.

Inhibitory deficits in the dorsolateral prefrontal cortex in psychopathic offenders.

Often typified as cunning social predators, psychopathic offenders show a persistent pattern of impulsive and reckless behavior, the pathophysiology of which has been related to dysfunction in the dorsolateral prefrontal cortex (DLPFC). That is, the DLPFC is important for the regulatory control of impulses and emotion as well as working memory and psychopathic offenders show impairments in all three dimensions. In the present study, we used combined transcranial magnetic stimulation and electroencephalography to compare the physiology of the DLPFC in 13 psychopathic offenders and 15 healthy subjects vis à vis excitability and inhibition. In addition, working memory performance was measured through the letter-number sequencing test. Results showed that compared to healthy subjects, psychopathic offenders had inhibition not excitability deficits in the DLPFC that was accompanied by deficits in working memory performance. In healthy controls and psychopathic offenders working memory performance correlated with the extent of inhibition over the DLPFC. Taken together, these findings suggest that psychopathic offenders suffer from dysfunctional inhibitory neurotransmission in the DLPFC and impaired working memory which may account for the behavioral impairments associated with this disorder.

Evidence for cortical inhibitory and excitatory dysfunction in obsessive compulsive disorder.

Several lines of evidence suggest that obsessive-compulsive disorder (OCD) is associated with an inability to inhibit unwanted intrusive thoughts. The neurophysiological mechanisms mediating such inhibitory deficits include abnormalities in cortical γ-aminobutyric acid (GABA) inhibitory as well as N-methyl-D-aspartate (NMDA) receptor-mediated mechanisms. Molecular evidence suggests that both these neurotransmitter systems are involved in OCD. Transcranial magnetic stimulation (TMS) represents a noninvasive technique to ascertain neurophysiological indices of inhibitory GABA and facilitatory NMDA receptor-mediated mechanisms. In this study, both mechanisms were indexed in 34 patients with OCD (23 unmedicated and 11 medicated) and compared with 34 healthy subjects. Cortical inhibitory and facilitatory neurotransmission was measured using TMS paradigms known as short-interval cortical inhibition (SICI), cortical silent period (CSP), and intracortical facilitation (ICF). Patients with OCD demonstrated significantly shortened CSP (p<0.001, Cohen's d=0.91) and increased ICF (p<0.009, Cohen's d=0.71) compared with healthy subjects. By contrast, there were no significant deficits in SICI. After excluding patients with OCD and comorbid major depressive disorder (MDD) from the analysis, these differences remained significant. Our findings suggest that OCD is associated with dysregulation in cortical inhibitory and facilitatory neurotransmission. Specifically, these findings suggest impairments in GABA(B) receptor-mediated and NMDA receptor-mediated neurotransmission. These findings are consistent with previously published genetic studies implicating GABA(B), and NMDA transporter and receptor genes in OCD. It is posited that dysregulation of such mechanisms may lead to the generation and persistence of intrusive thoughts that form the basis for this disorder.