Humberto Correa

Impulsive behavior in adults with attention deficit/ hyperactivity disorder: Characterization of attentional, motor and cognitive impulsiveness

Attention-deficit/hyperactivity disorder (ADHD) is characterized by inattention and/or hyperactivity/impulsivity. Impulsivity persists in adults with ADHD and might be the basis of much of the impairment observed in the daily lives of such individuals. The objective of this study was to address the presence, and more importantly, the three dimensions of impulsivity: attentional, non-planning and motor, in how they may relate to neuropsychological mechanisms of impulse control. We studied a sample of 50 adults with ADHD and 51 healthy comparison controls using the Barratt Impulsivity Scale Version 11 (BIS), and neuropsychological tasks, namely the Continuous Performance Task (CPT-II) and the Iowa Gambling Task (IGT). The ADHD group showed more signs of impulsivity on the three dimensions of BIS, committed more errors of omission and commission on the CPT-II, and made more disadvantageous choices on the IGT. These results support the existence of deficits related to three components of impulsivity: motor, cognitive, and attentional among adults with ADHD. Most importantly, this study also highlights the complementary nature of self-report questionnaires and neuropsychological tasks in the assessment of impulsivity in ADHD adults.

Suicide behavior and neuropsychological assessment of type I bipolar patients

BACKGROUND Neuropsychological deficits are often described in patients with bipolar disorder (BD). Some symptoms and/or associated characteristics of BD can be more closely associated to those cognitive impairments. We aimed to explore cognitive neuropsychological characteristics of type I bipolar patients (BPI) in terms of lifetime suicide attempt history. METHOD We studied 39 BPI outpatients compared with 53 healthy controls (HC) matched by age, educational and intellectual level. All subjects were submitted to a neuropsychological assessment of executive functions, decision-making and declarative episodic memory. RESULTS When comparing BDI patients, regardless of suicide attempt history or HC, we observed that bipolar patients performed worse than controls on measures of memory, attention, executive functions and decision-making. Patients with a history of suicide attempt performed worse than non-attempters on measures of decision-making and there were a significant negative correlation between the number of suicide attempts and decision-making results (block 3 and net score). We also found significant positive correlation between the number of suicide attempts and amount of errors in Stroop Color Word Test (part 3). LIMITATIONS The sample studied can be considered small and a potentially confounding variable - medication status - were not controlled. CONCLUSION Our results show the presence of neuropsychological deficits in memory, executive functions, attention and decision-making in BPI patients. Suicide attempts BPI scored worse than non-suicide attempt BPI on measures of decision-making. More suicide attempts were associated with a worse decision-making process. Future research should explore the relationship between the association between this specific cognitive deficits in BPIs, serotonergic function and suicide behavior in bipolar patients as well other diagnostic groups.

Decision-making impairment is related to serotonin transporter promoter polymorphism in a sample of patients with obsessive-compulsive disorder.

OBJECTIVE Decision-making impairment is an important feature of some psychiatric disorders, such as attention-deficit/hyperactivity disorder and substance-use disorders, and is associated with dysfunction of the fronto-subcortical circuit, mainly the orbitofrontal cortex (OFC). Several data reports support significant correlations between decision-making impairment and the serotonin system. Thus, this neurotransmission system may be a major step in some cognitive features, particularly in OCD because serotonin is associated with this disorder. Therefore, the serotonin transporter promoter polymorphism (5-HTTLPR) may be related to the modulation of these cognitive characteristics. In a sample of Caucasian OCD patients, we explored the link between decision-making and the 5-HTTLPR. METHOD We used the Iowa Gambling Task (IGT) to measure decision-making in 49 OCD patients, according to the DSM-IV criteria. All patients were submitted to Y-BOCS, BDI, BAI, the Raven Progressive Matrices, the Continuous Performance Task, and the Trail Making Test. We grouped S- and/or Lg-carriers in view of the fact that these act in a nearly dominant way. RESULTS On IGT, S- and/or Lg-carriers had significantly lower scores on the third, fourth, and fifth blocks. These findings were confirmed after adjusting for clinical and cognitive variables. DISCUSSION Inconclusive findings about the link between OCD and 5-HTTLPR may be better elucidated by studying OCD subgroups that could be more related in some genetic characteristics. Based on our study, low performance on IGT is associated with S- and/or Lg-carriers. CONCLUSION Our results corroborate the hypothesis that the pattern of neuropsychological functioning observed in previous studies may constitute a biological marker or heritable endophenotype of OCD.

Brazilian Portuguese version of the Iowa Gambling Task: transcultural adaptation and discriminant validity

OBJECTIVE The Iowa Gambling Task is a neuropsychological task developed in English, most widely used to assess decision-making. The aim of this work was to adapt the Iowa Gambling Task to Brazilian Portuguese, compare it with the original version and assess its validity. METHOD We assessed 75 Brazilian adults divided into three groups: 1) 25 healthy volunteers holding the Proficiency Certificate in English tested using the English version of the Iowa Gambling Task; 2) 25 healthy volunteers who did not speak or read English tested using the Iowa Gambling Task-Portuguese; 3) 25 Attention Deficit Hyperactivity Disorder subjects tested with the Iowa Gambling Task-Portuguese. RESULTS No difference between groups 1 and 2 was observed. Nonetheless, we found significant differences between Attention Deficit Hyperactivity Disorder subjects and the other 2 groups on blocks 3, 4, 5, and on net score. CONCLUSION Our results are similar to those previously described in the literature concerning adults without neuropsychiatric diseases. Since those two versions were equivalent and Attention Deficit Hyperactivity Disorder subjects performed significantly worse than healthy volunteers we can conclude that the adaptation of the Iowa Gambling Task to Brazilian Portuguese is valid and can be used for research purposes in the Brazilian context.

Prolactin response to d-fenfluramine and suicidal behavior in depressed patients

Previous studies of the prolactin response to D-fenfluramine in depressed patients have yielded inconsistent results. This may be because they did not address the question of suicidality. We carried out this study to test the hypothesis that lower prolactin response to D-fenfluramine is more closely associated with suicidal behavior than with depression itself. A D-fenfluramine test was performed in a sample of 18 healthy control subjects and in 85 drug-free inpatients with a DSM-III-R diagnosis of major depressive episode (49 with a history of suicide attempt, 36 without). Depressed inpatients with a history of suicide attempt showed a significantly lower prolactin response to D-fenfluramine compared to depressed inpatients without such a history and compared to control subjects. Healthy control subjects and depressed inpatients without a history of suicide attempt showed comparable levels of prolactin after D-fenfluramine. Time elapsed since suicide attempt did not influence prolactin level (baseline or post-stimulation). Results show that in our depressed drug-free inpatient sample, prolactin response to D-fenfluramine seems to be a marker of suicidality, but not of depression itself. We suggest that it is a trait marker of suicidality.

Is the 5-HTTLPR polymorphism associated with bipolar disorder or with suicidal behavior of bipolar disorder patients?

The serotonin transporter gene has a 44 bp insertion/deletion polymorphism within the promoter region (5‐HTTLPR) with two allelic forms, the long (L) and the short (S) variants. Association between the low‐activity S variant and bipolar disorder (BPD) has been shown but its replication has not been consistent. It has also been described as an association between the S allele and suicidal behavior. Since suicidal behavior is a rather frequent event in BPD, an important question is whether suicidality, instead of bipolarity itself, could be related to S allele. We assessed 351 subjects (167 bipolar inpatients and 184 healthy controls). Diagnosis was conducted by a psychiatrist using a structured interview (MINI‐PLUS), according to DSM‐IV criteria. Suicidal behavior was assessed using a semi‐structured instrument and a review of medical records. Genotyping of the 5‐HTTLPR was performed using PCR. There were 77 patients with a history of previous suicide attempts. Bipolar patients and healthy controls showed comparable genotypic and allelic frequencies. Patients carrying the S allele made violent suicide attempts more frequently (χ2 = 20.2; P = 0.0001) and made more suicide attempts (t = 2.6; P = 0.01). We were able to show an association between the S allele and suicidal behavior but not with BPD. Our data suggest that a phenotypic stratification, taking into account the suicidal behavior history, is of pivotal importance when performing association studies between BPD and 5‐HTTLPR genotypes, which could explain previous contradictory results.

Thyroid axis activity and serotonin function in major depressive episode

Abstract Recent studies in depression have reported alterations in both hypothalamic-pituitary-thyroid (HPT) axis activity and serotonin (5-HT) function; however, the functional relationships between the two systems have not been well defined in patients with major depressive episode. Thyrotropin (TSH) response to 0800 and 2300 h protirelin (TRH) challenges, and adrenocorticotropic hormone (ACTH), cortisol, and prolactin (PRL) responses to d -fenfluramine ( d -FEN), a specific 5-HT releasing/uptake-inhibiting agent, were examined in 60 drug-free DSM-IV major depressed inpatients and 20 hospitalized controls. Compared with controls, patients showed lower basal serum 2300 h TSH, 2300 h maximum increment in serum TSH above baseline (ΔTSH) and difference between 2300 h ΔTSH and 0800 h ΔTSH (ΔΔTSH) levels. The hormonal responses to d -FEN (i.e. ΔACTH, Δcortisol and ΔPRL) were interrelated. No significant difference in basal and post- d -FEN ACTH, cortisol or PRL values were found between controls and patients. A negative relationship between hormonal responses to d -FEN and 2300 h ΔTSH and ΔΔTSH values was observed in the depressed group. When patients were classified on the basis of their ΔTSH test status, patients with reduced ΔΔTSH values (i.e. with HPT axis abnormality) had hormonal d -FEN responses comparable to those of controls. Patients with normal ΔΔTSH values (i.e. without HPT axis abnormality) showed lower ACTH, cortisol and PRL responses to d -FEN than controls and patients with abnormal ΔΔTSH values. These results suggest that: (1) pathophysiological mechanisms other than 5-HT dysregulation may be involved in TSH blunting in major depressed patients; (2) 5-HT function is reduced in some depressed patients, especially those without HPT axis abnormality; and (3) HPT dysregulation may be regarded as a compensatory mechanism for diminished central 5-HT activity.

Neuropsychological assessment of impulsive behavior in abstinent alcohol-dependent subjects

OBJECTIVE Poor impulse control is thought to be one of the characteristics of alcohol addiction. The capacity to remain abstinent may be linked to cognitive bias related to three dimensions of impulsivity: motor, non-planning, and attentional impulsivity. The aim of this study was to evaluate the neuropsychological profile related to these impulsivity dimensions in alcohol-dependent patients within 15 -120 days of abstinence. METHOD We compared 31 alcohol-dependent patients to 30 matched healthy controls regarding their performances on the Continuous Performance Task, the Iowa Gambling Test, and the Wisconsin Card Sorting Test, each of which is thought to tax primarily one of the three dimensions of impulsivity just outlined. RESULTS When compared to controls, alcohol-dependent patients presented more commission errors on the Continuous Performance Task; made more disadvantageous choices on the Iowa Gambling Test; and made more perseverative errors on the Wisconsin Card Sorting Test. There was no significant correlation between performance on these tests and the length of abstinence. CONCLUSIONS These results suggest that deficits related to motor, non-planning and attentional components of impulsivity exist in alcohol-dependent patients, in the period immediately after acute alcohol withdrawal. These results may help guide interventions designed to prevent the risk of relapse in alcohol-abstinent patients.

Obsessive-compulsive disorder and immunology : A review

Interest in the possibility of an immune-mediated pathophysiology of obsessive-compulsive disorder and related disorders has increased. In the late 1980s, the National Institute of Mental Health reported an increase in obsessive-compulsive symptoms (OCS) in patients with Sydenham chorea (SC). Subsequently, a precipitating streptococcal infection in children with sudden onset of OCS but no chorea led to the coining of PANDAS (Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection). This association has furthered interest in biological measures for immune and genetic susceptibility in non-PANDAS obsessive-compulsive disorder patients (OCD). Furthermore, some studies are trying to demonstrate alterations of immune parameters in OCD patients, with few positive results. In this narrative review, our objective was to describe the immunologic findings in OCD, PANDAS, and their association with SC.

The leukocytes expressing DARPP-32 are reduced in patients with schizophrenia and bipolar disorder

Bipolar disorder (BPD) and schizophrenia (SCZ) are severe disorders representing an enormous social, familiar and individual burden, being SCZ the most disabling psychiatric disorder characterized by psychosis and cognitive impairment. It is well known that SCZ and BPD are associated with abnormalities in dopamine signaling pathway. Recent data in the literature have demonstrated altered expression levels of some proteins involved in the modulation of this pathway in both brain and peripheral tissues. It was shown that protein and mRNA levels of dopamine and cAMP regulated phosphoprotein (DARPP-32) were downregulated in dorsolateral prefrontal cortex (DLPFC) of patients with SCZ or BPD when compared to controls. Due to the difficulty to access brain tissue and the absence of objective laboratory tests for bio-markers, we measured DARPP-32 expression in blood cell sub-populations (CD4+ T lymphocytes, CD56+ NK cells, CD19+ B lymphocytes and CD14+ monocytes) taking advantage of the close relation of nervous and immune systems. Using flow cytometry as the analytical method, our results have shown that the DARPP-32 expression was diminished in CD4+ T lymphocytes, CD19+ B lymphocytes and CD14+ monocytes of BPD patients and was also decreased in CD4+ T lymphocytes and CD56+ NK cells of SCZ patients. These results showed that DARPP-32 expression in immune cells agrees with reports of reduced DARPP-32 protein in the DLPFC of BPD or SCZ patients. Our data suggest that DARPP-32 expression in PBMC could be used as a source of bio-markers to help in the treatment response of neuropsychiatry disorders as a window to the changes in the brain of those patients.