Suicidal ideation, suicide attempts, and psychological distress among intoxicated adolescents in the pediatric emergency department.

BACKGROUND: Studies have emphasized screening for psychiatric disorders, especially suicide risk in emergency departments. Psychiatric disorders and experimentation with alcohol increase in adolescence and intoxications among patients challenge the staff in emergency departments. AIMS: This study examined the degree of suicidal ideation (SI) and suicidal behavior in adolescents, and the extent to which they differed from non-suicidal patients in terms of alcohol use, psychological distress, self-esteem, and perceived social support. METHODS: The study comprised 120 adolescents, a mean age of 14.2 years. Of them 60% were females. We collected data on the clinical characteristics and assessed the patient's psychiatric status using self-report scales and analyzed blood samples for alcohol. A consulting psychiatrist interviewed each patient before discharge to evaluate potential SI or suicide attempt (SA) using structured and semi-structured scales. RESULTS: Of the 120 patients 20% had SI or had made a SA. High psychological distress in girls, low blood alcohol levels (BALs), as well as low scores on self-esteem, on social support and on familial support were associated with patients with SI/SA. Logistic regression showed that the most significant variables with suicidal patients included low BAL and low self-esteem and high alcohol consumption. Psychological distress had a direct and mediational role in the suicidal patients. CONCLUSIONS: Adolescents referred to the pediatric emergency department with intoxication displaying high psychological distress and low self-esteem represent a high-risk group of teens. In this group, careful assessment of mental health status, screening for suicidal ideation, and SAs seems warranted.

Methadone restores local and remote EEG functional connectivity in opioid-dependent patients.

Currently it has been proposed that normal brain function is critically dependent upon a dynamical balance between functions of local neuronal assemblies and global integrative processes. A loss of such metastable balance in favor of either independent or hyper-ordered processing is considered as the reflection of a brain disease. It has been shown that opioid dependence can be characterized as a disease of brain metastable balance, wherein local functional connectivity (synchronicity within neuronal assemblies) increased and remote functional connectivity (synchronicity between neuronal assemblies) decreased. Since methadone may be used as a maintenance treatment for opioid-dependent patients, the aim of this research was to study how methadone would influence the temporal and metastable cortical organization through the measures of local and remote electroencephalogram (EEG) functional connectivity in six opioid-depended patients who manage to complete at least six-month methadone treatment. The present study demonstrated that average parameters of temporal and metastable organization of the cortical dynamics (indexed by local and remote EEG functional connectivity) in such opioid-dependent patients did not differ from normal values of healthy subjects. We interpret these findings as a capability of the methadone to restore a normal temporal and metastable structure of brain activity in opioid-dependent patients after many months of methadone treatment. To our knowledge, present preliminary study is the first where the influence of methadone on temporal and metastable structure of EEG activity is demonstrated.

Opioid withdrawal results in an increased local and remote functional connectivity at EEG alpha and beta frequency bands.

Withdrawal may be a natural model to study craving and compulsive drug seeking, since craving can be viewed as a conditioned dysphoric state. It has been suggested that functional connectivity between brain areas may be of major value in explaining excessive craving and compulsive drug seeking by providing essential link between psychological and biological processes. Considering that withdrawal initiates a widespread activation of cortical regions responsible for compulsive drug seeking and desire for the drug, we predict that withdrawal would result in a significant increase in functional cortical connectivity. We applied the novel operational architectonics approach that enables us to estimate both local and remote functional cortical connectivity by means of EEG structural synchrony measure. In 13 withdrawal opioid-dependent patients we found the evidence that local and remote cortical functional connectivity was indeed significantly enhanced (for both alpha and beta frequency oscillations). Additionally, statistical relationship between functional connectivity and the severity of opioid withdrawal has been found.

Impaired pre-attentive auditory processing in opioid dependence with and without benzodiazepine co-dependence revealed by combined magnetoencephalography and electroencephalography.

Cognitive dysfunctions may be a significant factor in drug-seeking behavior, reducing the efficiency of rehabilitation in opioid dependence. Neurophysiological basis of these dysfunctions is poorly understood. 21 opioid-dependent patients and 15 healthy controls with no experience of illicit drugs were studied with simultaneous electroencephalography (EEG) and magnetoencephalography (MEG). Among opioid dependents 15 were benzodiazepine co-dependent. In a passive oddball paradigm, a train of 700-Hz standard tones (80%), presented to the left ear, was occasionally interrupted by infrequent deviants, which were either 600-Hz or 400-Hz pure tones or complex novel sounds. The auditory evoked potentials (AEP) and fields (AEF) were analyzed. The strength of the N1m dipoles was enhanced in patients with benzodiazepine co-dependence, but the latency of the response or the source location was not changed. A delay of mismatch negativity (MMN) response of novel tones in EEG, and delay of P3am response on the contralateral hemisphere to stimulated ear in MEG in opioid-dependent patients were observed. There were no differences in source locations or strengths of the dipoles for P1m, MMNm, and P3am determined using equivalent current dipoles. There were no group differences in EEG amplitude measures. In conclusion, our results suggest delayed pre-attentive auditory processing of novel information in opioid dependence. Benzodiazepine co-dependence modulated N1m response.

Composition of EEG oscillations and their temporal characteristics: methadone treatment.

In this study, we examine the composition of electroencephalographic (EEG) oscillations within a broad frequency band (0.5-30 Hz) for opioid abuse (22 patients), during withdrawal (13 patients), and after 6 months of methadone treatment (6 patients) and in 14 healthy subjects during a resting condition (closed eyes). The exact compositions of EEG oscillations and their temporal behaviour were assessed using the probability-classification analysis of short-term EEG spectral patterns. The study reveals the dynamics of particular EEG oscillations throughout the conditions of opioid dependency, withdrawal and methadone-based treatment. It was shown that methadone maintenance treatment normalized considerably the composition of EEG oscillations and their percentage ratio and restored the temporal structure of patients' EEG comparable with healthy subjects. The importance of the methadone's ability to restore a normal temporal structure of the brain's activity is discussed.

Increased local and decreased remote functional connectivity at EEG alpha and beta frequency bands in opioid-dependent patients.

RATIONALE: Although researchers now have a working knowledge of key brain structures involved in realization of actions of substance abuse and addiction, deeper understanding will require examination of network interactions between cortical neuronal assemblies and their subcortical tails in the effects of opioid dependence. OBJECTIVES: Given that repeated exposure to opiates initiates a widespread reorganization of cortical regions, we predict that opioid dependence would result in a considerable reorganization of local and remote functional connectivity in the neocortex. METHODS: We applied the novel operational architectonics approach that enables us to estimate two local and remote functional cortex connectivities by means of electroencephalogram structural synchrony measure. RESULTS: In 22 opioid-dependent patients, we found the evidence that brain functional connectivity was indeed disrupted by chronic opioid abuse (i.e., the local functional connectivity increased and remote functional connectivity decreased in opioid abusers). This significant difference between "opioid" and "control" populations was the same for alpha and beta frequency bands. Additionally, significant negative relations between duration (years) of daily opioid abuse and the number/strength of functional connections in the posterior section of the cortex were found.

Reorganization of the composition of brain oscillations and their temporal characteristics in opioid dependent patients.

In the present study, we examined the composition of electroencephalographic (EEG) brain oscillations in broad frequency band (0.5-30 Hz) in 22 opioid-dependent patients and 14 healthy subjects during resting condition (closed eyes). The exact compositions of brain oscillations and their temporal behavior were assessed by the probability-classification analysis of short-term EEG spectral patterns. It was demonstrated that EEG of patients with opioid dependence was characterized by (a) significant reorganization of brain oscillations with increase in the percentage of beta- and mostly fast-alpha-rhythmic segments, (b) longer periods of temporal stabilization for alpha and beta brain oscillations and by shorter periods of temporal stabilization for theta and polyrhythmic activity when compared with control subjects, and (c) right-sided dominance (significantly larger relative presence of particular spectral patterns in EEG channels of the right hemisphere). These effects were widely distributed across the cortex with the maximum magnitude in the occipital, right parietal, temporal, and frontal areas. Taken together the present study suggested (a) an allostatic state with neuronal activation, and (b) high sensitivity of the right hemisphere to adverse opioid effects.

Cognitive function during early abstinence from opioid dependence: a comparison to age, gender, and verbal intelligence matched controls.

BACKGROUND: Individuals with opioid dependence have cognitive deficits during abuse period in attention, working memory, episodic memory, and executive function. After protracted abstinence consistent cognitive deficit has been found only in executive function. However, few studies have explored cognitive function during first weeks of abstinence. The purpose of this study was to study cognitive function of individuals with opioid dependence during early abstinence. It was hypothesized that cognitive deficits are pronounced immediately after peak withdrawal symptoms have passed and then partially recover. METHODS: Fifteen patients with opioid dependence and fifteen controls matched for, age, gender, and verbal intelligence were tested with a cognitive test battery When patients performed worse than controls correlations between cognitive performance and days of withdrawal, duration of opioid abuse, duration of any substance abuse, or opioid withdrawal symptom inventory score (Short Opiate Withdrawal Scale) were analyzed. RESULTS: Early abstinent opioid dependent patients performed statistically significantly worse than controls in tests measuring complex working memory, executive function, and fluid intelligence. Their complex working memory and fluid intelligence performances correlated statistically significantly with days of withdrawal. CONCLUSION: The results indicate a rather general neurocognitive deficit in higher order cognition. It is suggested that cognitive deficit during early abstinence from opioid dependence is related to withdrawal induced neural dysregulation in the prefrontal cortex and is partly transient.

Magnetic resonance imaging of severe, long-term, opiate-abuse patients without neurologic symptoms may show enlarged cerebrospinal spaces but no signs of brain pathology of vascular origin.

BACKGROUND: Recreational drug abuse is one of the most important risk factors for stroke in young adults. Abuse of opiates may lead to severe acute neurologic problems due to ischemia or hemorrhage. In contrast, their minor effects on brain structures are not well established. We evaluated brain magnetic resonance images (MRI) of opiate-dependent subjects who had no major neurologic symptoms or psychiatric disorder. METHODS: Seventeen opiate-dependent patients and 17 controls underwent 1.5 T MRI. Any abnormalities in signal intensity of the brain were recorded. Areas of vermis, corpus callosum, and midline internal skull surface (MISS) were measured from midline sagittal slice. To evaluate size of cortical sulci, sylvian fissures, and ventricles, axial images were compared with standard sets of reference images. In addition, bifrontal and sylvian-fissure ratios were measured. RESULTS: Only one patient had a small subcortical post-traumatic lesion; otherwise, gray and white matter showed normal signal intensities. Opiate-dependent subjects had significantly wider sylvian fissures (p=0.008, Mann-Whitney U) and larger ventricles (p=0.04) than controls. Bifrontal and sylvian-fissure ratios were significantly higher in patient group than in controls (p=0.013 and p=0.005, respectively). CONCLUSIONS: No signs of brain pathology of vascular origin were found. From the clinical point of view, we want to emphasize that in the first acute neurologic attack of opiate-dependent patients, any abnormal signal intensity in MRI is most probably associated with the patient's current situation. Sylvian fissures and ventricles were wider in opiate-dependent subjects than in controls, which may be related to brain atrophy located especially in frontal and temporal lobes.

Cerebral measurements and their correlation with the onset age and the duration of opioid abuse.

BACKGROUND: Opioid-dependent patients have been shown to have structural brain alterations. This study focuses on magnetic resonance imaging (MRI) measurements of brain and their correlation with the onset age and the duration of opioid abuse. METHODS: Brain MRI was obtained from 17 opioid-dependent patients (mean age 34 years, SD 7 years) and 17 controls. Compulsive opioid use had begun between ages 15 and 31 (mean 20) and had continued from 5 to 26 years. All patients were tobacco smokers, six had also abused amphetamines and 11 benzodiazepines. Relative volumes of cerebral white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) spaces were measured. In addition, Sylvian fissure ratio (SFR), bifrontal ratio, and midsagittal cerebellar vermian area were correlated with the onset age and the duration of opioid abuse. RESULTS: The total volume (GM + WM + CSF) of the cerebrum was significantly smaller in patients than in controls (Mann-Whitney U-test, p = 0.026) as well as the absolute volumes of GM and WM (p = 0.014 and p = 0.007, respectively). There was no significant difference in GM and WM volumes normalized with total cerebral volume. In contrast, the absolute volume of CSF did not significantly differ between the groups, but the relative volume of CSF was significantly higher in opioid dependents (p = 0.029). SFR and bifrontal ratio were larger in opioid dependents than in controls (p = 0.005 and p = 0.013). The SFR correlated negatively (p = 0.017, r = - 0.569) and the area of vermis cerebelli correlated positively (p = 0.043, r = 0.496) with the onset age of opioid abuse. The length of opioid abuse and the area of vermis cerebellum had a negative correlation (p = 0.038, r = - 0.523) even though the areas of cerebellar vermis did not significantly differ between opioid dependents and controls. The authors speculate that the onset of substance abuse in adolescence or early adulthood may have in part disturbed the late brain maturation process, as in normal development, the dorsolateral frontal cortex and superior parts of the temporal lobes are the last to maturate. Also, the cerebellar vermis may be affected by early onset substance abuse. It is possible that the brain is more vulnerable to substance abuse at a young age than later in life.

Do individuals with former amphetamine dependence have cognitive deficits?

The association between former amphetamine dependence and cognitive performance was studied in a sample of 12 individuals with former amphetamine dependence who had been abstinent for at least 1 year and in 12 age-, gender- and verbal IQ-matched controls. The groups were compared by cognitive tests on attention, memory, executive function and fluid intelligence. Individuals with former amphetamine dependence performed significantly poorer than controls in memory domain. Follow-up analysis of variance showed minor deficits in tests of delayed verbal memory. The results remained essentially the same when participants with current DSM-IV axis I diagnosis were excluded from the analysis. It is concluded that individuals with former amphetamine dependence have normal cognitive function with the possible exception of verbal memory. Thus, if widespread cognitive deficits are found in individuals with former amphetamine dependence, etiologies other than amphetamine abuse as such should be carefully investigated.