Dentin decalcification during lithium treatment: case report.

Severe dental decay and changes in tooth structure have been reported in association with the use of lithium in Psychiatry, but lithium effects on tooth inorganic composition remain unknown. A 30-year-old woman with bipolar disorder, treated with lithium carbonate presented severe dental decay. Dentin samples from lithium and healthy volunteers were collected and submitted to ionic and ultrastructural analysis. Samples from the lithium patient exhibited irregular peritubular walls and the mineral crystals were irregularly arranged in the intertubular dentin. In addition, a decrease in Mg/P/Ca and an increase of Zn concentrations were detected. These data suggest that the severe dental decay and changes in the tooth structure observed for the lithium-treated patient are related to dentin mineral loss and that this pathological condition is different from caries lesions.

Family-based association analysis of serotonin genes in pathological gambling disorder: evidence of vulnerability risk in the 5HT-2A receptor gene.

Pathological gambling (PG) has become a growing public health problem in many countries around the world. PG is an impulse control disorder and its behavior and psychopathology present similarities with substance abuse disorders. Evidence from twin studies supports a significant genetic predisposition to PG, but the precise genetic loci still remain unclear. The present study investigates the allele and genotype distribution of polymorphisms of the serotonin transporter, serotonin receptor 1B and 2A genes in 140 sib-pairs discordant for the diagnosis of PG. A significant association of the C/C genotype of the serotonin receptor 2A T102C (rs 6313) polymorphism and the PG phenotype was observed [OR = 1.7 (1.1-3.4)]. This preliminary result is consistent with the hypothesis that the serotonin system is associated with addiction behavior and similar results have been reported for nicotine and alcohol dependence.

Superior antidepressant efficacy results of agomelatine versus fluoxetine in severe MDD patients: a randomized, double-blind study.

The objective of this international, 8-week, randomized, double-blind study was to show the superiority of the antidepressant efficacy of agomelatine, the first MT1/MT2 receptor agonist and 5-HT2C receptor antagonist antidepressant, versus fluoxetine in outpatients fulfilling Diagnostic and Statistical Manual of Mental Disorders-volume IV-TR criteria for major depressive disorder of severe intensity, defined by a baseline Hamilton Depression Rating Scale (HAM-D17) total score of at least 25 and CGI severity of illness score of at least 4. Patients received agomelatine 25-50 mg/day (n=252) or fluoxetine 20-40 mg/day (n=263) for 8 weeks. The main efficacy outcome measure was HAM-D17 total score (change from baseline to last post-baseline assessment). Secondary outcome measures were Clinical Global Impressions-improvement (CGI), severity (CGI-S), anxiety (HAM-A), and sleep (HAM-D sleep items) scores. The mean decrease in HAM-D17 total score over 8 weeks was significantly greater with agomelatine than fluoxetine with a between-group difference of 1.49 (95% confidence interval, 0.20-2.77; P=0.024). The percentage of responders at last post-baseline assessment was higher with agomelatine on both HAM-D17 (decrease in total score from baseline ≥50%; 71.7% agomelatine vs. 63.8% fluoxetine; P=0.060) and CGI-improvement (score 1 or 2; 77.7 vs. 68.8%; P=0.023). There was a significant between-group difference of 0.37 (95% confidence interval, 0.06-0.68) in HAM-D sleep subscore in favor of agomelatine (P=0.018). Similar improvements were observed on HAM-A with agomelatine and fluoxetine. Both treatments were safe and well tolerated. In conclusion, in this study, agomelatine showed superior antidepressant efficacy over fluoxetine in treating patients with a severe episode of major depressive disorder after 8 weeks of treatment with a good tolerability profile.

Cognitive control associated with irritability induction: an autobiographical recall fMRI study.

OBJECTIVE: Despite the relevance of irritability emotions to the treatment, prognosis and classification of psychiatric disorders, the neurobiological basis of this emotional state has been rarely investigated to date. We assessed the brain circuitry underlying personal script-driven irritability in healthy subjects (n = 11) using functional magnetic resonance imaging. METHOD: Blood oxygen level-dependent signal changes were recorded during auditory presentation of personal scripts of irritability in contrast to scripts of happiness or neutral emotional content. Self-rated emotional measurements and skin conductance recordings were also obtained. Images were acquired using a 1,5T magnetic resonance scanner. Brain activation maps were constructed from individual images, and between-condition differences in the mean power of experimental response were identified by using cluster-wise nonparametric tests. RESULTS: Compared to neutral scripts, increased blood oxygen level-dependent signal during irritability scripts was detected in the left subgenual anterior cingulate cortex, and in the left medial, anterolateral and posterolateral dorsal prefrontal cortex (cluster-wise p-value < 0.05). While the involvement of the subgenual cingulate and dorsal anterolateral prefrontal cortices was unique to the irritability state, increased blood oxygen level-dependent signal in dorsomedial and dorsal posterolateral prefrontal regions were also present during happiness induction. CONCLUSION: Irritability induction is associated with functional changes in a limited set of brain regions previously implicated in the mediation of emotional states. Changes in prefrontal and cingulate areas may be related to effortful cognitive control aspects that gain salience during the emergence of irritability.

Cognitive control associated with irritability induction: an autobiographical recall fMRI study / Controle cognitivo associado à indução de irritabilidade: um estudo de RMf usando recordações autobiográficas

OBJECTIVE: Despite the relevance of irritability emotions to the treatment, prognosis and classification of psychiatric disorders, the neurobiological basis of this emotional state has been rarely investigated to date. We assessed the brain circuitry underlying personal script-driven irritability in healthy subjects (n = 11) using functional magnetic resonance imaging. METHOD: Blood oxygen level-dependent signal changes were recorded during auditory presentation of personal scripts of irritability in contrast to scripts of happiness or neutral emotional content. Self-rated emotional measurements and skin conductance recordings were also obtained. Images were acquired using a 1,5T magnetic resonance scanner. Brain activation maps were constructed from individual images, and between-condition differences in the mean power of experimental response were identified by using cluster-wise nonparametric tests. RESULTS: Compared to neutral scripts, increased blood oxygen level-dependent signal during irritability scripts was detected in the left subgenual anterior cingulate cortex, and in the left medial, anterolateral and posterolateral dorsal prefrontal cortex (cluster-wise p-value < 0.05). While the involvement of the subgenual cingulate and dorsal anterolateral prefrontal cortices was unique to the irritability state, increased blood oxygen level-dependent signal in dorsomedial and dorsal posterolateral prefrontal regions were also present during happiness induction. CONCLUSION: Irritability induction is associated with functional changes in a limited set of brain regions previously implicated in the mediation of emotional states. Changes in prefrontal and cingulate areas may be related to effortful cognitive control aspects that gain salience during the emergence of irritability.

OBJETIVO: Apesar da relevância de emoções de irritabilidade para o tratamento, prognóstico e classificação dos transtornos psiquiátricos, as bases neurobiológicas deste tipo de estado emocional foram raramente investigadas até hoje. Este estudo avaliou os circuitos cerebrais subjacentes à irritabilidade induzida por scripts pessoais em voluntários saudáveis (n = 11) usando ressonância magnética funcional. MÉTODO: Mudanças no sinal dependente do nível de oxigenação sanguínea (blood-oxygen level dependent signal) foram registradas durante a apresentação por via auditiva de scripts pessoais de irritabilidade em contraste com scripts de felicidade ou de conteúdo emocional neutro. Escores em escalas de autoavaliação emocional e medidas de condutância da pele também foram obtidos. A aquisição de imagens foi realizada em aparelho de ressonância magnética de 1,5 T. Os mapas de ativação cerebral foram construídos a partir das imagens individuais, e as diferenças entre as condições experimentais foram investigadas utilizando testes não-paramétricos baseados em permutações. RESULTADOS: Em comparação com scripts neutros, a apresentação de scripts de irritabilidade levou a aumentos de sinal dependente do nível de oxigenação sanguínea na porção subgenual do giro do cíngulo anterior esquerdo e nas porções medial, ântero-lateral e póstero-lateral do córtex pré-frontal dorsal (cluster-wise p-valor < 0,05). Enquanto o envolvimento do cíngulo anterior subgenual e do córtex pré-frontal dorsal antero-lateral surgiu apenas em associação com o estado de irritabilidade, aumentos do sinal dependente do nível de oxigenação sanguínea nas porções dorso-medial e dorsal póstero-lateral do córtex pré-frontal também estiveram presentes durante indução de felicidade. CONCLUSÃO: Indução de irritabilidade está associada a mudanças de atividade funcional num conjunto restrito de regiões cerebrais previamente implicadas na mediação de estados emocionais. Mudanças na atividade...

Bipolar disorder and concurrent psychiatric and medical disorders.

A correct diagnosis of bipolar disorder is crucial to determining appropriate treatment strategies, but the majority of patients with this illness are initially misdiagnosed. Bipolar presentations share features with other psychiatric disorders such as unipolar depression and borderline personality disorder, and comorbid medical conditions further complicate diagnosis. Clinicians may minimize diagnostic and treatment issues by focusing on differential diagnosis and dual treatment of bipolar disorder and co-occurring conditions. The physical health of patients with bipolar disorder should be monitored, because this population is at risk for obesity, metabolic syndrome, and associated conditions.

Introduction to bipolar disorder and comorbid conditions.

Bipolar disorder presents with symptoms that overlap with other, often comorbid, psychiatric disorders, such as borderline personality disorder, substance use disorder, and unipolar depression, and also often co-occurs with medical disorders. Appropriate screening for manic and hypomanic symptoms may lessen the frequency of misdiagnosis of bipolar disorder as unipolar depression, which has serious treatment implications. Further, following the appropriate guidelines for monitoring the physical health of patients with bipolar disorder, especially those treated with mood stabilizers and atypical antipsychotic agents, is important to achieve optimal outcomes.

Validity of a frustration-induction procedure

OBJECTIVE: To test a reliable and easily administered frustration-induction procedure for experimental research. METHOD: One hundred volunteers (81 women, mean age ± SD 34.2 ± 8 years) physically and psychiatrically healthy submitted to the frustration induction procedure were prevented from reaching reward level scores. Subjective aggressiveness feelings related to frustration were self-rated in a 13-item visual analogue scale before and after the procedure. RESULTS: Significant increases in aggressiveness-related feelings were detected in 12 of the 13 items. This was consistent with the observed overt behavior of the subjects during the task. CONCLUSIONS: The frustration-induction procedure is a simple, easy to administer frustration-induction procedure that can be used in experimental studies in normal subjects.

OBJETIVO: Testar um procedimento de indução de frustração confiável e de simples aplicação para a pesquisa experimental. MÉTODO: Cem voluntários (81 mulheres, idade média ± DP 34,2 ± 8 anos), física e psiquiatricamente saudáveis, submetidos ao procedimento de indução de frustração, foram impedidos de atingir escores de recompensa. Os sentimentos de agressividade subjetivos relacionados à frustração foram autoclassificados em um escala analógica visual de 13 itens antes e após o procedimento. RESULTADOS: Foram detectados aumentos significativos nos sentimentos relacionados à agressividade em 12 dos 13 itens. Isto foi consistente com o comportamento manifestado pelos indivíduos e observado durante a tarefa. CONCLUSÕES: O procedimento de indução de frustração é simples, facilmente aplicável e que pode ser utilizado em estudos experimentais com indivíduos normais.

Validity of a frustration-induction procedure.

OBJECTIVE: To test a reliable and easily administered frustration-induction procedure for experimental research. METHOD: One hundred volunteers (81 women, mean age +/- SD 34.2 +/- 8 years) physically and psychiatrically healthy submitted to the frustration induction procedure were prevented from reaching reward level scores. Subjective aggressiveness feelings related to frustration were self-rated in a 13-item visual analogue scale before and after the procedure. RESULTS: Significant increases in aggressiveness-related feelings were detected in 12 of the 13 items. This was consistent with the observed overt behavior of the subjects during the task. CONCLUSIONS: The frustration-induction procedure is a simple, easy to administer frustration-induction procedure that can be used in experimental studies in normal subjects.

Effect of chronic treatment with clomipramine on food intake, macronutrient selection and body weight gain in rats.

Long-term treatment with clomipramine (CMI), a tricyclic antidepressant, induces food craving and body weight gain in patients. The present study investigated the effects of chronic treatment with CMI on total food intake, macronutrient selection, and body weight gain in rats. Male Wistar rats were maintained on a dietary self-selection regime with separate sources of protein, fat and carbohydrate. Animals received i.p. injections of CMI (0, 3, 10, 30 mg/kg) during 27 consecutive days. Food consumption and body weight were recorded daily and results were calculated as average of three consecutive days, namely during pre-treatment (3 d before pharmacological treatment), treatment (7th-9th; 16th-18th and 25th-27th days), and post-treatment (28th-33rd days). Results showed that CMI (30 mg/kg) significantly decreased energy intake during all treatment period, an effect that was related to a decrease in both carbohydrate-rich diet intake and body weight gain. At dose of 3 mg/kg CMI increased the total energy intake in the 16th-18th days, suggesting an apparent biphasic effect of chronic treatment with CMI on caloric intake. Chronic administration with CMI (27 d) did not alter protein-rich or fat-rich diet consumption. The main result of this study indicated that chronic treatment with CMI decreases rather than increase food consumption and body weight gain in rats exposed to a macronutrient self-selection procedure.

Pathological gambling and obsessive-compulsive disorder: towards a spectrum of disorders of volition.

OBJECTIVE: Pathological gambling is proposed as a participant of an impulsive-compulsive spectrum related to obsessive-compulsive disorder. This study aims to contrast pathological gambling and obsessive-compulsive disorder regarding course, comorbidity, and personality, hence testing the validity of the impulsive-compulsive spectrum. METHOD: 40 pathological gambling and 40 obsessive-compulsive disorder subjects matched to 40 healthy volunteers according to gender, age, and education were assessed with the Temperament Personality Questionnaire and the Barratt Impulsiveness Scale. Psychiatric patients were also assessed for course and comorbidity data. RESULTS: Obsessive-compulsive disorder presented an earlier onset, but the full syndrome took longer to evolve. Pathological gambling had higher comorbidity with substance-related disorders, and obsessive-compulsive disorder higher comorbidity with somatoform disorders. Gamblers scored higher than controls on the sub-factors Impulsiveness, Extravagance, Disorderliness, and Fear of Uncertainty. Obsessive-compulsive patients scored higher than controls on Fear of Uncertainty. Impulsiveness, Extravagance, and Disorderliness significantly correlated with the Barratt Impulsiveness Scale total score, Fear of Uncertainty did not. DISCUSSION: The course and comorbidity profiles of pathological gambling resemble an addiction and differ from obsessive-compulsive disorder. Pathological gambling combines impulsive and compulsive traits. Impulsivity and compulsivity should be regarded as orthogonal constructs, and as drives implicated in volition aspects of behavioral syndromes.

Oxidative stress parameters in unmedicated and treated bipolar subjects during initial manic episode: a possible role for lithium antioxidant effects.

Studies have proposed the involvement of oxidative stress and neuronal energy dysfunctions in the pathophysiology of bipolar disorder (BD). This study evaluates plasma levels of the oxidative/energy metabolism markers, thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), and neuron-specific enolase (NSE) during initial episodes of mania compared to controls in 75 subjects. Two groups of manic subjects (unmedicated n=30, and lithium-treated n=15) were age/gender matched with healthy controls (n=30). TBARS and antioxidant enzymes activity (SOD and CAT) were increased in unmedicated manic patients compared to controls. Conversely, plasma NSE levels were lower during mania than in the controls. In contrast, acute treatment with lithium showed a significant reduction in both SOD/CAT ratio and TBARS levels. These results suggest that initial manic episodes are associated with both increased oxidative stress parameters and activated antioxidant defenses, which may be related to dysfunctions on energy metabolism and neuroplasticity pathways. Antioxidant effects using lithium in mania were shown, and further studies are necessary to evaluate the potential role of these effects in the pathophysiology and therapeutics of BD.

Pathological gambling and obsessive-compulsive disorder: towards a spectrum of disorders of volition

OBJECTIVE: Pathological gambling is proposed as a participant of an impulsive-compulsive spectrum related to obsessive-compulsive disorder. This study aims to contrast pathological gambling and obsessive-compulsive disorder regarding course, comorbidity, and personality, hence testing the validity of the impulsive-compulsive spectrum. METHOD: 40 pathological gambling and 40 obsessive-compulsive disorder subjects matched to 40 healthy volunteers according to gender, age, and education were assessed with the Temperament Personality Questionnaire and the Barratt Impulsiveness Scale. Psychiatric patients were also assessed for course and comorbidity data. RESULTS: Obsessive-compulsive disorder presented an earlier onset, but the full syndrome took longer to evolve. Pathological gambling had higher comorbidity with substance-related disorders, and obsessive-compulsive disorder higher comorbidity with somatoform disorders. Gamblers scored higher than controls on the sub-factors Impulsiveness, Extravagance, Disorderliness, and Fear of Uncertainty. Obsessive-compulsive patients scored higher than controls on Fear of Uncertai-nty. Impulsiveness, Extravagance, and Disorderliness significantly correlated with the Barratt Impulsiveness Scale total score, Fear of Uncertainty did not. DISCUSSION: The course and comorbidity profiles of pathological gambling resemble an addiction and differ from obsessive-compulsive disorder. Pathological gambling combines impulsive and compulsive traits. Impulsivity and compulsivity should be regarded as orthogonal constructs, and as drives implicated in volition aspects of behavioral syndromes.

OBJETIVO: Propõe-se que o jogo patológico faça parte de um espectro impulsivo-compulsivo relacionado ao transtorno obsessivo-compulsivo. O presente estudo propõe-se a comparar o jogo patológico e o transtorno obsessivo-compulsivo em relação a curso, comorbidade e personalidade, a fim de testar a validade do espectro impulsivo-compulsivo. MÉTODO: Quarenta jogadores e 40 portadores de transtorno obsessivo-compulsivo pareados a 40 voluntários normais de acordo com gênero, idade e nível educacional foram avaliados através do Questionário de Temperamento e Caráter e da Escala de Impulsividade de Barratt. Para os pacientes, dados sobre curso da doença e comorbidade psiquiátrica também foram avaliados. RESULTADOS: O transtorno obsessivo-compulsivo apresentou início mais precoce, mas o desenvolvimento da síndrome completa foi mais longo. O jogo patológico teve comorbidade mais elevada com transtornos pelo uso de substâncias, e o transtorno obsessivo-compulsivo teve maior comorbidade com transtornos somatoformes. Os jogadores tiveram escores mais elevados do que os controles nos subfatores Impulsividade, Extravagância e Desorganização, e Medo da Incerteza. Os pacientes obsessivo-compulsivos tiveram escores mais elevados do que os controles em Medo da Incerteza. Impulsividade, Extravagância e Desorganização se correlacionaram significativamente com o escore total na Escala de Impulsividade de Barratt, enquanto Medo da Incerteza não. DISCUSSÃO: O perfil de curso e comorbidade do jogo patológico se parece com o de uma dependência, diferindo do transtorno obsessivo-compulsivo. O jogo patológico combina traços impulsivos e compulsivos. Impulsividade e compulsividade são construtos ortogonais e implicados nos aspectos volitivos das síndromes comportamentais.