Callosal abnormalities, altered cortisol levels, and neurocognitive deficits associated with early maltreatment among adolescents: A voxel-based diffusion-tensor imaging study.

INTRODUCTION: Neuroimaging studies have shown callosal abnormalities among maltreated subjects, but little is known about the functional and neurobiological correlates of these supposed developmental alterations. The aim of this study was to investigate childhood maltreatment (CM), neurocognitive functioning, cortisol levels, and corpus callosum (CC) integrity among adolescents. METHODS: One hundred and seven subjects underwent magnetic resonance imaging (MRI) with voxel-based diffusion-tensor imaging (DTI) and the Crossed Finger Localization Test (CFLT). Psychopathology was investigated with the Schedule for Affective Disorders and Schizophrenia (K-SADS-PL); CM was detailed by the Childhood Trauma Questionnaire (CTQ), and salivary cortisol levels were measured by immunoassay. RESULTS: Higher levels of CM were associated with current lower CFLT scores, mainly in the CROSSED condition, involving interhemispheric communication of sensorimotor information (p < .05) and with reduced fractional anisotropy (FA) in the splenium of the CC (p < .01). Deficits in the CFLT were also associated with higher cortisol levels (p < .05). CONCLUSION: The association among CM, neuropsychological abnormalities, callosal microstructure alterations, and cortisol levels suggests an altered pattern of brain interhemispheric connectivity among maltreated adolescents. Further studies are needed to investigate the extent to which these sensorimotor deficits and abnormal cortisol levels may be possible mediators of negative neurodevelopmental trajectories and adult psychopathology.

Distinct effects of cocaine and cocaine + cannabis on neurocognitive functioning and abstinence: A six-month follow-up study.

BACKGROUND AND AIMS: Cannabis use is frequent among individuals with cocaine use disorder. Despite recent non-controlled studies advocating a therapeutic role of smoked cannabis, there is a paucity of evidence-based data on potential therapeutic and cognitive side-effects of this association. METHODS: We examined 63 cocaine-addicted subjects who used cannabis more than 50 times in lifetime (COC + CAN), 24 cocaine-addicted patients who use cannabis less than 50 times (COC), and 36 controls (CON). Participants were evaluated with an extensive battery of neurocognitive tests after two weeks of supervised detoxification in an inpatient treatment program. Patients were followed up in one, three, and six months after discharge. RESULTS: Both groups of patients performed worse than CON on working memory, processing speed, inhibitory control, mental flexibility, and decision making. COC + CAN performed worse than COC on speed processing, inhibitory control and sustained attention, while COC performed worse than COC + CAN on mental flexibility. Concomitant cannabis use did not decrease relapses to cocaine use after one, three and six months. Among COC + CAN, earlier cocaine and cannabis use, and impaired executive functioning were predictive of relapse on cocaine after six months. CONCLUSION: Our results did not support the recommendation of smoked cannabis as a safe therapeutic approach for cocaine-addicted patients due to significant negative cognitive side-effects and absence of efficacy. Further studies investigating frontal brain morphology, neuromaturation, and prescription of the non-psychoactive constituent of cannabis sativa cannabidiol among cocaine-addicted patients who use cannabis are warranted.

The role of neurocognitive functioning, substance use variables and the DSM-5 severity scale in cocaine relapse: A prospective study.

BACKGROUND: The severity of substance use disorder (SUD) is currently defined by the sum of DSM-5 criteria. However, little is known about the validity of this framework or the role of additional severity indicators in relapse prediction. This study aimed to investigate the relationship between DSM-5 criteria, neurocognitive functioning, substance use variables and cocaine relapse among inpatients with cocaine use disorder (CUD). METHODS: 128 adults aged between 18 and 45 years were evaluated; 68 (59 males, 9 females) had CUD and 60 (52 males, 8 females) were healthy controls. For the group with CUD, the use of other substances was not an exclusion criterion. Participants were tested using a battery of neurocognitive tests. Cocaine relapse was evaluated 3 months after discharge. RESULTS: Scores for attention span and working memory were worse in patients compared to controls. Earlier onset and duration of cocaine use were related to poorer inhibitory control and global executive functioning, respectively; recent use was related to worse performance in inhibitory control, attention span and working memory. More DSM-5 criteria at baseline were significantly associated with relapse. CONCLUSIONS: Recent cocaine use was the most predictive variable for neurocognitive impairments, while DSM-5 criteria predicted cocaine relapse at three months post treatment. The integration of neurocognitive measures, DSM-5 criteria and cocaine use variables in CUD diagnosis could improve severity differentiation. Longitudinal studies using additional biomarkers are needed to disentangle the different roles of severity indicators in relapse prediction and to achieve more individualized and effective treatment strategies for these patients.

The route of administration exacerbates prefrontal functional impairments in crack cocaine users.

Studies have evidenced more severe health consequences in individuals who smoked crack cocaine as compared to intranasal cocaine users. Differential neurocognitive deficits between the crack and intranasal cocaine-addicted patients, associated with prefrontal cortex functions, have never been tested using complex cognitive tasks in humans. In this study, we examined possible distinct neurocognitive deficits in 43 crack-addicted patients (CrD) compared with 36 intranasal cocaine-addicted patients (CD) and 32 controls. CrD and CD were evaluated after 2 weeks of supervised detoxification in two inpatient treatment programs. All the subjects were evaluated using an extensive battery of neurocognitive tasks, including the Trail Making Test, the Stroop Color-Word Test, the Digits Forward and Digits Backward tasks, the Controlled Oral Word Association Test, the Wechsler Adult Intelligence Scale, and the Frontal Assessment Battery. Differences in performance in the neurocognitive tests between the three groups were investigated controlling for age, IQ, psychiatric symptoms, and years of education. Both intranasal and crack users were impaired on a variety of cognitive measures relative to controls. Crack users performed worse than intranasal cocaine users in inhibitory control (p < .05) and general executive functioning (p < .01). Crack use seems to be more deleterious to neurocognitive functions associated with the prefrontal cortex. This may predispose crack-addicted patients to more severe negative clinical outcomes. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Distinct cognitive performance and patterns of drug use among early and late onset cocaine users.

INTRODUCTION: Adolescence is a crucial period for neurodevelopment, but few studies have investigated the impact of early cocaine use on cognitive performance and patterns of substance use. METHODS: We evaluated 103 cocaine dependent inpatients divided in two groups: early-onset users (EOG; n=52), late-onset users (LOG; n=51), and 63 healthy controls. Neuropsychological functioning was evaluated using Digits Forward (DF) and Backward (DB), Trail Making Test (TMT), Stroop Color Word Test (SCWT), Controlled Oral Word Association Test (COWAT), Wisconsin Card Sorting Test (WCST), Rey Osterrieth Complex Figure Test (ROCFT), Frontal Assessment Battery (FAB), and Iowa Gambling Test (IGT). Use of alcohol and other drugs was assessed with the Addiction Severity Index (ASI-6). RESULTS: Analyses of covariance controlling for age, IQ and years of education showed that EOG presented worse performance in attention span (DF, p=0.020), working memory (DB, p=0.001), sustained attention (WCST, p=0.030), declarative memory (ROCFT, p=0.031) and general executive functioning (FAB, p=0.003) when compared with the control group. LOG presented impairments on divided attention (TMT, p=0.003) and general executive functioning (FAB, p=0.001) in relation to the control group. EOG presented higher use of cannabis and alcohol than LOG (p≤0.001). CONCLUSION: Early-onset cocaine users display more pronounced neuropsychological alterations than controls, as well as a greater frequency of polydrug consumption than LOG. The prominent cognitive deficits in EOG probably reflect the deleterious interference of cocaine use with early stages of neurodevelopment. This may be related to more severe clinical characteristics of substance disorder in this subgroup, including polysubstance abuse.

Social skills and psychopathic traits in maltreated adolescents.

Child maltreatment has frequently been associated with impaired social skills and antisocial features, but there are still controversies about the effect of each type of maltreatment on social behaviour. The aim of this study was to compare the social functioning and psychopathic traits of maltreated adolescents (MTA) with a control group (CG) and to investigate what types of maltreatments and social skills were associated with psychopathic traits in both groups. The types and intensity of maltreatment were evaluated through the Childhood Trauma Questionnaire (CTQ) in 107 adolescents, divided into the MTA group (n = 66) and non-maltreated youths (n = 41), our CG. The Hare Psychopathy Checklist: Youth Version (PCL: YV) and a detailed inventory for evaluation of social skills in adolescents were also applied in all individuals. MTA presented more psychopathic traits than the CG, in all domains measured by PCL: YV, independently of IQ levels and the presence of psychiatric disorders. Interestingly, the groups did not differ significantly from each other on indicators of social skills. Multiple regression analysis revealed that emotional neglect was the only maltreatment subtype significantly associated with psychopathic traits, more specifically with the PCL: YV interpersonal factor (F1), and that some social skills (empathy, self-control and social confidence) were related to specific psychopathic factors. The results highlight that emotional neglect may be more detrimental to social behaviours than physical and sexual abuse, and that neglected children require more specific and careful attention.

Motivational interviewing combined with chess accelerates improvement in executive functions in cocaine dependent patients: a one-month prospective study.

BACKGROUND: In cocaine-dependent individuals, executive function (EF) deficits are associated with poor treatment outcomes. Psychological interventions and pharmacological approaches have produced only modest effect sizes. To date, studies of this topic have been few and limited. The aim of this study was to examine the effects of a new model of intervention, which integrates chess and Motivational Interviewing, Motivational Chess (MC) METHODS: We evaluated 46 cocaine-dependent inpatients (aged 18-45), in two groups-MC (n=26); and active comparison-AC (n=20). Using neuropsychological tests and an impulsivity scale, we assessed the subjects before and after the study period (one month of abstinence monitored by urine toxicology screening). RESULTS: The MC and AC groups did not differ at baseline. In the post-intervention assessment (after one month), both groups showed significant improvements in attention, mental flexibility, inhibitory control, abstraction abilities, and decision-making (p<0.01). In addition, the improvement in working memory was more significant in the MC group than in the AC group (group-by-time interaction, p=01). CONCLUSIONS: One month of abstinence was sufficient to improve various attentional and executive domains in cocaine-dependent subjects. The MC intervention was associated with greater improvements in EFs, especially working memory, suggesting that tailored interventions focusing on complex EFs accelerate the process of cognitive recovery during the initial period of abstinence.

Executive cognitive dysfunction and ADHD in cocaine dependence: searching for a common cognitive endophenotype for addictive disorders.

BACKGROUND: Cocaine-dependent individuals (CDI) present executive cognitive function (ECF) deficits, but the impact of psychiatric comorbidities such as Attention-Deficit Hyperactivity Disorder (ADHD) on neuropsychological functioning is still poorly understood. The aim of this study was to investigate if CDI with ADHD (CDI + ADHD) would have a distinct pattern of executive functioning when compared with CDI without ADHD (CDI). METHODS: We evaluated 101 adults, including 69 cocaine-dependent subjects (divided in CDI and CDI + ADHD) and 32 controls. ECF domains were assessed with Digits Forward (DF), Digits Backward (DB), Stroop Color Word Test (SCWT), the Wisconsin Card Sorting Test (WCST), and the Frontal Assessment Battery (FAB). DSM-IV criteria for ADHD were used for diagnosis and previous ADHD symptoms (in the childhood) were retrospectively assessed by the Wender-Utah Rating Scale (WURS). RESULTS: There were no significant differences between CDI + ADHD, CDI, and controls in estimated intellectual quotient (IQ), socioeconomic background, education (in years), and pre-morbid IQ (p > 0.05). SCWT and WCST scores did not differ across groups (p > 0.05). Nevertheless, CDI and CDI + ADHD performed more poorly than controls in total score of the FAB (p < 0.05). Also, CDI + ADHD did worse than CDI on DF (F = 4.756, p = 0.011), DB (F = 8.037, p = 0.001), Conceptualization/FAB (F = 4.635, p = 0.012), and Mental flexibility/FAB (F = 3.678, p = 0.029). We did not find correlations between cocaine-use variables and neuropsychological functioning, but previous ADHD symptoms assessed by WURS were negatively associated with DF (p = 0.016) and with the total score of the FAB (p = 0.017). CONCLUSION: CDI + ADHD presented more pronounced executive alterations than CDI and CDI exhibited poorer cognitive functioning than controls. Pre-existing ADHD symptoms may have a significant negative impact on executive dysfunction in CDI. It remains to be investigated by future studies if symptoms such as impulsivity or a pre-existing ECF dysfunction could represent underlying cognitive endophenotypes that would substantially increase the risk for acquiring addictive disorders.

31P-spectroscopy of frontal lobe in schizophrenia: alterations in phospholipid and high-energy phosphate metabolism.

Studies using 31P-magnetic resonance spectroscopy (MRS) reported on abnormalities in frontal lobe metabolism in schizophrenia. The most consistent findings were a reduction in the resonances of phosphomonoesters (PME) and/or increased phosphodiesters (PDE), which are, respectively, the precursors and the metabolites of membrane phospholipids, thus suggesting an accelerated phospholipid metabolism in the disease. Other studies reported increased high-energy phosphates (ATP-adenosine triphosphate and PCr-phosphocreatine) in schizophrenia, reflecting decreased use of energy in the frontal lobe. We investigated 53 schizophrenic patients (DSM-IV) and 35 healthy controls. Eighteen from these patients were drug nai;ve and the remaining 35 were drug-free for an average of 6 months. Phospholipid metabolism and high-energy phosphates were assessed in the left frontal lobe using 31P-MRS. Psychopathological evaluation was done with the Brief Psychiatric Rating Scale (BPRS) and the Negative Symptoms Rating Scale (NSRS). Neuropsychological evaluation was performed with the Wisconsin Card Sorting Test (WCST), Stroop Test and Wechsler Adult Intelligence Scale. Drug-nai;ve patients showed reduced PDE in the left frontal lobe compared to controls and to previously medicated patients (p<0.05). No differences among the three groups were found regarding the other spectroscopy parameters. In healthy controls, but not in schizophrenics, a negative (and probably physiological) correlation was found between PME and PDE (p<0.01). In schizophrenic patients, ATP was correlated with negative symptoms and with neuropsychological impairment (p<0.01). The lack of a correlation between PME and PDE, as well as the reduction of PDE in schizophrenia, suggest a disrupted phospholipid metabolism in the disease, albeit on a contrary direction of that reported in literature. The relationships of ATP with negative symptoms and neuropsychological deficit suggest an alteration of energetic demand in the frontal lobe of schizophrenic patients, which is in line with the hypofrontality hypothesis of the disease.