Suicidality, self-harm and psychotic-like symptoms in a general adolescent psychiatric sample.

AIM: We investigated the associations between clinical high-risk for psychosis (CHR), psychotic-like symptoms and suicidality among adolescent psychiatric patients. METHODS: The sample consisted of 54 CHR and 107 non-CHR psychiatric patients aged 15-18 in Helsinki, Finland, who were assessed at the beginning of their psychiatric treatment with the Structured Interview for Prodromal Syndromes (SIPS). Current suicidality was measured with the Beck Depression Inventory (item 9), while lifetime suicidality was evaluated from all available data, including patient files. The participants were followed for 2.8-8.9 years via the national hospital discharge register, with the follow-up outcome being intentional self-harm. Data on suicides were also gathered from the Causes of Death statistics. RESULTS: Only 30.5% of the adolescents had no suicidal ideation at the beginning of their treatment. CHR risk state and SIPS-assessed delusions, suspiciousness, and hallucinations were associated with higher current suicidality. Of the 154 adolescents with register follow-up, there were five (3.2%) with intentional self-harm resulting in hospital treatment, all female. CHR status was not associated with self-harm. Current suicidality, familial risk of psychosis, and SIPS decreased expression of emotions were associated with self-harm during follow-up. In a Cox regression analysis model among girls, only decreased expression of emotions remained a significant predictor of intentional self-harm. Baseline suicidality measures were not associated with transitions to psychosis. CONCLUSIONS: CHR status was associated with higher current suicidality but did not predict follow-up intentional self-harm in treatment-seeking adolescents. Decreased expression of emotions may indicate higher risk of intentional self-harm in adolescent treatment-seeking girls.

Evaluation of verbal list learning as a predictor of psychosis.

AIM: We explored whether cognitive performance, and verbal learning in particular, predicts psychosis or psychiatric hospitalizations among unselected first-admission adolescent patients in general psychiatric care. METHODS: Up to 152 adolescents aged 15-18 were interviewed with the SIPS, tested with a cognitive test battery in the beginning of their psychiatric treatment, and followed for a maximum of 9 years (median 4.5 years). RESULTS: The composite factors of processing speed, verbal performance and visuospatial performance did not predict psychosis (n = 7) or all-cause psychiatric hospitalizations (n = 26) beyond psychosis risk symptoms. However, those who developed psychosis performed worse on California Verbal Learning Test (CVLT) compared to other adolescents. Lower scores of CVLT immediate recall predicted psychosis (P = .003, HR = 1.13 per CVLT point decrease). However, when general verbal ability was adjusted for, CVLT did not reach significance. CONCLUSIONS: Impaired verbal list learning may predict psychosis also among adolescent psychiatric patients not preselected for psychosis risk suspicion.

Predicting psychosis in a general adolescent psychiatric sample.

INTRODUCTION: Current psychosis risk criteria have often been studied on a pre-selected population at specialized clinics. We investigated whether the Structured Interview for Prodromal Syndromes (SIPS) is a useful tool for psychosis risk screening among adolescents in general psychiatric care. METHODS: 161 adolescents aged 15-18 with first admission to adolescent psychiatric services in Helsinki were interviewed with the SIPS to ascertain Clinical High-Risk (CHR) state. The participants were followed via the national hospital discharge register, patient files, and follow-up interviews. DSM-IV Axis I diagnoses were made at baseline and 12 months. Register follow-up spanned 2.8-8.9 years, and hospital care for a primary psychotic disorder and any psychiatric disorder were used as outcomes. RESULTS: CHR criteria were met by 54 (33.5%) of the adolescents. Three conversions of psychosis as defined by SIPS emerged during follow-up, two of whom belonged to the CHR group. The positive predictive value of the CHR status was weak (1.9%) but its negative predictive value was 98.0%. Using the DSM-IV definition of psychosis, there were five conversions, three of which were in the CHR group. In regression analyses, hospital admissions for primary psychotic disorder were predicted by positive symptom intensity in the baseline SIPS. In addition, CHR status and SIPS positive and general symptoms predicted hospitalization for psychiatric disorder. DISCUSSION: Psychosis incidence was low in our unselected sample of adolescent psychiatric patients. CHR status failed to predict SIPS or DSM-IV psychoses significantly at 12 months. However, in a longer follow-up, CHR did predict psychiatric hospitalization.

Outcome predictors for problem drinkers treated with combined cognitive behavioral therapy and naltrexone.

BACKGROUND: The opioid antagonist naltrexone, combined with cognitive behavioural therapy (CBT), has proven efficacious for patients with alcohol dependence, but studies examining how this treatment works in a naturalistic treatment setting are lacking. OBJECTIVES: This study examined predictors of the outcome of targeted naltrexone and CBT in a real-life outpatient setting. Participants were 315 patients who attended a treatment program providing CBT combined with the targeted use of naltrexone. METHODS: Mixture models for estimating developmental trajectories were used to examine change in patients' alcohol consumption and symptoms of alcohol craving from treatment entry until the end of the treatment (20 weeks) or dropout. Predictors of treatment outcome were examined with analyses of multinomial logistic regression. Minimal exclusion criteria were applied to enhance the generalizability of the findings. RESULTS: Regular drinking pattern, having no history of previous treatments, and high-risk alcohol consumption level before the treatment were associated with less change in alcohol use during the treatment. The patients with low-risk alcohol consumption level before the treatment had the most rapid reduction in alcohol craving. Patients who drank more alcohol during the treatment had lower adherence with naltrexone. CONCLUSION: Medication non-adherence is a major barrier to naltrexone's effectiveness in a real-life treatment setting. Patients with more severe alcohol problems may need more intensive treatment for achieving better treatment outcome in real-word treatment settings.

Association between Neurocognitive Impairment and the Short Allele of the 5-HTT Promoter Polymorphism in Depression: A Pilot Study.

Depression has been shown to be associated with cognitive deficits in various cognitive domains. However, it is still unclear which factors contribute to cognitive impairment. The objective of this study was to find out whether a functional polymorphism in the promoter region of the serotonin transporter (5-HTTLPR) gene is associated with the impairment of cognitive functioning among depressed patients. In a pilot study, a sample of 19 patients with major depressive disorder (MDD) and 19 healthy controls was investigated with an extensive psychiatric and neuropsychological examination. All participants were genotyped for 5-HTTLPR. Depressed patients with the short allele of the 5-HTT promoter region exhibited inferior cognitive performance compared to patients with the long allele polymorphism. In healthy controls, no association between genotype and cognitive performance was found. The result suggests that in MDD patients with the short allele of the 5-HTTLPR polymorphism the vulnerability to cognitive impairment is increased compared to MDD patients without the short allele inheritance. These preliminary findings need to be confirmed in a larger cohort of MDD patients.

Low verbal ability predicts later violence in adolescent boys with serious conduct problems.

BACKGROUND: Delinquent adolescents are a known high-risk group for later criminality. Cognitive deficits correlate with adult criminality, and specific cognitive deficits might predict later criminality in the high-risk adolescents. AIMS: This study aimed to explore the neuropsychological performance and predictors of adult criminal offending in adolescents with severe behavioural problems. METHODS: Fifty-three adolescents (33 boys and 20 girls), aged 15-18 years, residing in a reform school due to serious conduct problems, were examined for neuropsychological profile and psychiatric symptoms. Results were compared with a same-age general population control sample, and used for predicting criminality 5 years after the baseline testing. RESULTS: The reform school adolescents' neuropsychological performance was weak on many tasks, and especially on the verbal domain. Five years after the baseline testing, half of the reform school adolescents had obtained a criminal record. Males were overrepresented in both any criminality (75% vs. 10%) and in violent crime (50% vs. 5%). When cognitive variables, psychiatric symptoms and background factors were used as predictors for later offending, low verbal intellectual ability turned out to be the most significant predictor of a criminal record and especially a record of violent crime. CONCLUSIONS: Neurocognitive deficits, especially in the verbal and attention domains, are common among delinquent adolescents. Among males, verbal deficits are the best predictors for later criminal offending and violence. CLINICAL IMPLICATIONS: Assessing verbal abilities among adolescent population with conduct problems might prove useful as a screening method for inclusion in specific therapies for aggression management.

Do drug treatment variables predict cognitive performance in multidrug-treated opioid-dependent patients? A regression analysis study.

BACKGROUND: Cognitive deficits and multiple psychoactive drug regimens are both common in patients treated for opioid-dependence. Therefore, we examined whether the cognitive performance of patients in opioid-substitution treatment (OST) is associated with their drug treatment variables. METHODS: Opioid-dependent patients (N = 104) who were treated either with buprenorphine or methadone (n = 52 in both groups) were given attention, working memory, verbal, and visual memory tests after they had been a minimum of six months in treatment. Group-wise results were analysed by analysis of variance. Predictors of cognitive performance were examined by hierarchical regression analysis. RESULTS: Buprenorphine-treated patients performed statistically significantly better in a simple reaction time test than methadone-treated ones. No other significant differences between groups in cognitive performance were found. In each OST drug group, approximately 10% of the attention performance could be predicted by drug treatment variables. Use of benzodiazepine medication predicted about 10% of performance variance in working memory. Treatment with more than one other psychoactive drug (than opioid or BZD) and frequent substance abuse during the past month predicted about 20% of verbal memory performance. CONCLUSIONS: Although this study does not prove a causal relationship between multiple prescription drug use and poor cognitive functioning, the results are relevant for psychosocial recovery, vocational rehabilitation, and psychological treatment of OST patients. Especially for patients with BZD treatment, other treatment options should be actively sought.

Cognitive functioning in opioid-dependent patients treated with buprenorphine, methadone, and other psychoactive medications: stability and correlates.

BACKGROUND: In many but not in all neuropsychological studies buprenorphine-treated opioid-dependent patients have shown fewer cognitive deficits than patients treated with methadone. In order to examine if hypothesized cognitive advantage of buprenorphine in relation to methadone is seen in clinical patients we did a neuropsychological follow-up study in unselected sample of buprenorphine- vs. methadone-treated patients. METHODS: In part I of the study fourteen buprenorphine-treated and 12 methadone-treated patients were tested by cognitive tests within two months (T1), 6-9 months (T2), and 12-17 months (T3) from the start of opioid substitution treatment. Fourteen healthy controls were examined at similar intervals. Benzodiazepine and other psychoactive comedications were common among the patients. Test results were analyzed with repeated measures analysis of variance and planned contrasts. In part II of the study the patient sample was extended to include 36 patients at T2 and T3. Correlations between cognitive functioning and medication, substance abuse, or demographic variables were then analyzed. RESULTS: In part I methadone patients were inferior to healthy controls tests in all tests measuring attention, working memory, or verbal memory. Buprenorphine patients were inferior to healthy controls in the first working memory task, the Paced Auditory Serial Addition Task and verbal memory. In the second working memory task, the Letter-Number Sequencing, their performance improved between T2 and T3. In part II only group membership (buprenorphine vs. methadone) correlated significantly with attention performance and improvement in the Letter-Number Sequencing. High frequency of substance abuse in the past month was associated with poor performance in the Letter-Number Sequencing. CONCLUSIONS: The results underline the differences between non-randomized and randomized studies comparing cognitive performance in opioid substitution treated patients (fewer deficits in buprenorphine patients vs. no difference between buprenorphine and methadone patients, respectively). Possible reasons for this are discussed.

Short cognitive behavioral therapy and cognitive training for adults with ADHD - a randomized controlled pilot study.

In clinical practice, a growing need exists for effective non-pharmacological treatments of adult attention-deficit/hyperactivity disorder (ADHD). Here, we present the results of a pilot study of 10 adults with ADHD participating in short-term individual cognitive- behavioral therapy (CBT), 9 adults participating in cognitive training (CT), and 10 controls. Self-report questionnaires, independent evaluations, and computerized neurocognitive testing were collected before and after the treatments to evaluate change. There were distinctive pre-hypotheses regarding the treatments, and therefore the statistical comparisons were conducted in pairs: CBT vs control, CT vs control, and CBT vs CT. In a combined ADHD symptom score based on self-reports, 6 participants in CBT, 2 in CT and 2 controls improved. Using independent evaluations, improvement was found in 7 of the CBT participants, 2 of CT participants and 3 controls. There was no treatment-related improvement in cognitive performance. Thus, in the CBT group, some encouraging improvement was seen, although not as clearly as in previous research with longer interventions. In the CT group, there was improvement in the trained tasks but no generalization of the improvement to the tasks of the neurocognitive testing, the self- report questionnaires, or the independent evaluations. These preliminary results warrant further studies with more participants and with more elaborate cognitive testing.

The relationship between psychotic-like symptoms and neurocognitive performance in a general adolescent psychiatric sample.

INTRODUCTION: The current criteria for detecting a Clinical High-Risk (CHR) state for psychosis do not address cognitive impairment. A first step for identifying cognitive markers of psychosis risk would be to determine which aspects of neurocognitive performance are related with more severe psychotic-like symptoms. This study assessed cognitive impairment associated with prodromal symptoms in adolescents receiving public psychiatric treatment. METHODS: 189 adolescents were recruited from consecutive new patients aged 15-18 attending mainly outpatient adolescent psychiatric units in Helsinki. They had been screened for prodromal symptoms using the Prodromal Questionnaire, and all screen-positives as well as a random sample of screen-negatives were interviewed using the Structured Interview for Prodromal Symptoms (SIPS) and underwent testing using a large, standardized neurocognitive test battery. The sample included 62 adolescents who met the CHR criteria (CHR) and 112 who did not (non-CHR). A healthy control sample (n=72) was also included to provide age- and gender-matched norms. RESULTS: The CHR group performed worse on visuospatial tasks than the non-CHR group. Among CHR adolescents, negative symptoms were associated with slower processing speed and poorer performance on verbal tasks. Among non-CHR adolescents, positive symptoms were associated with poorer performance on visuospatial tasks, and negative symptoms with poorer performance on verbal tasks. CONCLUSION: Clinical high-risk status is associated with impaired visuospatial task performance. However, both positive, psychotic-like symptoms and negative symptoms are associated with lower levels of neurocognitive functioning among adolescents in psychiatric treatment regardless of whether CHR criteria are met. Thus, even mild positive and negative symptoms may have clinical relevance in adolescents in psychiatric care. Adolescents with both psychotic-like symptoms and neurocognitive deficits constitute a group requiring special attention.

Lack of association between neuropsychological performance and level of psychosis-proneness in an adolescent psychiatric sample.

Studies of the prodromal stage of schizophrenia show that the late prepsychotic phase is associated with mild neuropsychological deficits that parallel those of schizophrenia. However, it is still unclear whether this association is present across the whole range of symptoms of psychosis-proneness, or specific to the extreme groups. In this study, the linear associations between dimensions of psychosis-proneness (as measured by the 92-item Prodromal Questionnaire) and performance on 20 neuropsychological measures were assessed in a group of 71 nonpsychotic adolescent psychiatric patients. A structure of positive, negative and disorganized prodromal symptom dimensions was found, replicating earlier findings. No symptom dimension was significantly associated with neuropsychological performance, even when corrected for nonspecific psychological distress. These findings suggest that the association between symptoms and neuropsychological performance is specific to high levels of symptoms or to the truly prodromal subpopulation. The results also highlight the importance of simultaneous assessment of affective state.

Clarifying the diversity of first-episode psychosis: Neuropsychological correlates of clinical symptoms.

BACKGROUND: Psychosis is marked by heterogeneity, which complicates effective treatment. AIMS: Subgroups of first-episode psychosis could be found by identifying neuropsychological correlates of psychiatric symptoms. METHODS: Ninety-two outpatients with first-episode psychosis were evaluated with the Positive and Negative Syndrome Scale (PANSS) and a comprehensive neuropsychological test battery. RESULTS: Factor analysis of PANSS revealed five symptom dimensions. Negative symptoms were correlated with widespread neuropsychological dysfunction. Disorganization symptoms were correlated with more focused deficits in executive function, attention and processing speed implicating dysfunction in frontal-subcortical circuits. Asocial, positive and affective symptoms were not associated with cognition. CONCLUSIONS: In first-episode psychosis, neuropsychological deficits are associated with negative and disorganization symptom dimensions, which appear to be marked by different cognitive profiles. These findings have implications for improving symptom-specific treatment.

Memory function in opioid-dependent patients treated with methadone or buprenorphine along with benzodiazepine: longitudinal change in comparison to healthy individuals.

BACKGROUND: Opioid-substitution treatment (OST) for opioid dependence (OD) has proven effective in retaining patients in treatment and reducing illegal opiate abuse and crime. Consequently, the World Health Organization (WHO) has listed the opioid agonists methadone and buprenorphine as essential drugs for OD that should be available worldwide. In many areas of the world, OD is often associated with concomitant benzodiazepine (BZD) dependence and abuse, which complicates treatment. However, possible changes in the cognitive functioning of these patients are not well-known. The present study is the first to examine longitudinal stability of memory function in OST patients with BZD use, thus providing a new tool for health policy authorities in evaluating the usefulness of OST. METHODS: Within the first two months (T1) and between 6-9 months (T2) after OST admission, we followed the working memory, immediate verbal memory, and memory consolidation of 13 methadone- and 15 buprenorphine- or buprenorphine/naloxone-treated patients with BZD dependence or abuse disorder. The results were compared to those of fifteen normal comparison participants. All participants also completed a self-reported memory complaint questionnaire on both occasions. RESULTS: Both patient groups performed statistically significantly worse than normal comparison participants in working memory at time points T1 and T2. In immediate verbal memory, as measured by list learning at T1, patients scored lower than normal comparison participants. Both patient groups reported significantly more subjective memory problems than normal comparison participants. Patients with more memory complaints recalled fewer items at T2 from the verbal list they had learned at T1 than those patients with fewer memory complaints. The significance of the main analyses remained nearly the same when the statistical tests were performed without buprenorphine-only patients leaving 12 patients to buprenorphine/naloxone group. CONCLUSION: Working memory may be persistently affected in OST patients with BZD use. A high number of memory complaints among OST patients with BZD use may indicate memory consolidation impairment. These findings show that recovery of memory function in OD patients treated along with BZDs takes time, and their memory complaints may have practical relevance.

Longitudinal cognitive decline in subcortical ischemic vascular disease--the LADIS Study.

BACKGROUND: Cross-sectional studies have indicated that subcortical ischemic vascular disease (SIVD), as defined according to imaging criteria, is associated with a specific clinical and cognitive profile. Much less is known about the long-term cognitive consequences of SIVD. The aim of the study was to investigate the longitudinal cognitive performance and incident dementia in subjects with and without SIVD in a sample of older adults with white matter lesions. METHODS: In the Leukoaraiosis and Disability (LADIS) study, 639 participants were examined with annual clinical and neuropsychological evaluations for 3 years. The subjects meeting the MRI criteria of SIVD at baseline were compared to the other subjects of the sample with linear mixed models. RESULTS: The overall level of cognitive performance over the follow-up period was inferior in multiple cognitive domains in SIVD subjects as compared to the reference group. The subjects with SIVD presented significantly steeper decline of performance in the Stroop test (parts I and II), Trail Making A test, Verbal fluency test, and Mini-Mental State Examination. They also had a threefold risk of developing dementia during follow-up independently of age, sex, education and medial temporal lobe atrophy. CONCLUSIONS: SIVD, as a manifestation of cerebral small vessel disease, is related to progressive cognitive impairment and a considerable risk of developing dementia. SIVD seems to specifically contribute to the deterioration of psychomotor speed, executive control, and global cognitive function.

MRI-defined subcortical ischemic vascular disease: baseline clinical and neuropsychological findings. The LADIS Study.

BACKGROUND: Subcortical ischemic vascular disease (SIVD) is a common, but often overlooked cause of vascular cognitive impairment. Diagnostic research criteria for SIVD are based on magnetic resonance imaging (MRI) findings including substantial white matter lesions (WML) and multiple lacunar infarcts. Empirical studies validating these imaging criteria are still few. The purpose of the study was to describe the clinical and cognitive characteristics of the MRI-defined SIVD in a mixed sample of functionally independent elderly subjects with WML. METHODS: The subjects of the Leukoaraiosis and Disability (LADIS) study, aged 65-84 years, underwent comprehensive clinical and neuropsychological examinations, and brain MRI at the baseline assessment. The subjects meeting the SIVD imaging criteria (n = 89) were compared to the other subjects of the sample (n = 524). RESULTS: SIVD was associated with lower education, hypertension and, independently, with obesity. The subjects with SIVD had more often motor impairment, a history of falls, and subtle impairment in activities of daily living, but they did not differ for depressive symptoms. SIVD subjects performed significantly inferiorly in tests of global cognitive function, psychomotor speed, attention and executive functions, verbal fluency, and working memory. CONCLUSION: In this population of nondisabled older adults with WML, SIVD was related to specific clinical and functional characteristics. Neuropsychological features included psychomotor slowing as well as deficits in attention and executive functions.

White matter lesions are related to impaired instrumental activities of daily living poststroke.

BACKGROUND: White matter lesions (WMLs) are frequent in elderly people, and have been associated with impaired activities of daily living (ADL) and cognitive decline. We sought to examine the role of WMLs and their extent, in regard to basic ADL, instrumental ADL (IADL), and cognitive functions, in a large well-defined cohort examined 3 months after an ischemic stroke. METHODS: The study group included 395 of 486 consecutive patients aged 55 to 85 years who, 3 months after an ischemic stroke, completed a neuropsychological test battery and magnetic resonance imaging, and structured medical, neurological, and laboratory evaluations; assessment included an interview with a knowledgeable informant. RESULTS: The patients with the most severe WMLs (n = 213) were older, in comparison with those with moderate (n = 71) or mild/no (n = 111) WMLs. These patients also more often had Diagnostic and Statistical Manual of Mental Disorders, Third Edition dementia; had a lower Mini Mental Status score; were more often women; more often had impaired immediate and delayed memory performance, executive dysfunction, and impaired basic ADL and IADL functions; and had more infarcts and cortical or central atrophy in magnetic resonance imaging. However, there were no significant differences among the 3 groups in stroke severity measured on the Scandinavian Stroke Scale, in stroke-related depression as measured by the Beck Depression Inventory, or in stroke type. According to multiple logistic regression analysis, higher age (odds ratio 1.067, 95% confidence interval 1.036-1.01) and impaired IADL (odds ratio 0.852, 95% confidence interval 0.778-0.931) significantly correlated with severe WMLs. CONCLUSIONS: Although the degree of WMLs was not associated with stroke severity, it was associated with global cognitive function, impaired memory functions, executive dysfunction, sex, and impaired basic ADL. Age and IADL functions were independent correlates of severe WMLs.

Methadone vs. buprenorphine/naloxone during early opioid substitution treatment: a naturalistic comparison of cognitive performance relative to healthy controls.

BACKGROUND: Both methadone- and buprenorphine-treated opioid-dependent patients frequently show cognitive deficits in attention, working memory, and verbal memory. However, no study has compared these patient groups with each other during early opioid substitution treatment (OST). Therefore, we investigated attention, working memory, and verbal memory of opioid-dependent patients within six weeks after the introduction of OST in a naturalistic setting and compared to those of healthy controls. METHODS: The sample included 16 methadone-, 17 buprenorphine/naloxone-treated patients, and 17 healthy controls matched for sex and age. In both groups buprenorphine was the main opioid of abuse during the recent month. Benzodiazepine codependence, recent use, and comedication were also common in both patient groups. Analysis of variance was used to study the overall group effect in each cognitive test. Pair-wise group comparisons were made, when appropriate RESULTS: Methadone-treated patients, as a group, had significantly slower simple reaction time (RT) compared to buprenorphine/naloxone-treated patients. In Go/NoGo RT methadone patients were significantly slower than controls. Both patient groups were significantly debilitated compared to controls in working memory and verbal list learning. Only methadone patients were inferior to controls in story recall. In simple RT and delayed story recall buprenorphine/naloxone patients with current benzodiazepine medication (n = 13) were superior to methadone patients with current benzodiazepine medication (n = 13). When methadone patients were divided into two groups according to their mean dose, the patient group with a low dose (mean 40 mg, n = 8) showed significantly faster simple RT than the high dose group (mean 67 mg, n = 8). CONCLUSION: Deficits in attention may only be present in methadone-treated early phase OST patients and may be dose-dependent. Working memory deficit is common in both patient groups. Verbal memory deficit may be more pronounced in methadone-treated patients than in buprenorphine/naloxone-treated patients. In sum, to preserve cognitive function in early OST, the use of buprenorphine/naloxone may be more preferable to methadone use of, at least if buprenorphine has been recently abused and when benzodiazepine comedication is used. Longitudinal studies are needed to investigate if the better performance of buprenorphine/naloxone-treated patients is a relatively permanent effect or reflects "only" transient opioid switching effect.

Corpus callosum atrophy is associated with mental slowing and executive deficits in subjects with age-related white matter hyperintensities: the LADIS Study.

BACKGROUND: Previous research has indicated that corpus callosum atrophy is associated with global cognitive decline in neurodegenerative diseases, but few studies have investigated specific cognitive functions. OBJECTIVE: To investigate the role of regional corpus callosum atrophy in mental speed, attention and executive functions in subjects with age-related white matter hyperintensities (WMH). METHODS: In the Leukoaraiosis and Disability Study, 567 subjects with age-related WMH were examined with a detailed neuropsychological assessment and quantitative magnetic resonance imaging. The relationships of the total corpus callosum area and its subregions with cognitive performance were analysed using multiple linear regression, controlling for volume of WMH and other confounding factors. RESULTS: Atrophy of the total corpus callosum area was associated with poor performance in tests assessing speed of mental processing--namely, trail making A and Stroop test parts I and II. Anterior, but not posterior, corpus callosum atrophy was associated with deficits of attention and executive functions as reflected by the symbol digit modalities and digit cancellation tests, as well as by the subtraction scores in the trail making and Stroop tests. Furthermore, semantic verbal fluency was related to the total corpus callosum area and the isthmus subregion. CONCLUSIONS: Corpus callosum atrophy seems to contribute to cognitive decline independently of age, education, coexisting WMH and stroke. Anterior corpus callosum atrophy is related to the frontal-lobe-mediated executive functions and attention, whereas overall corpus callosum atrophy is associated with the slowing of processing speed.

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.