Effects of lithium and valproate on behavioral parameters and neurotrophic factor levels in an animal model of mania induced by paradoxical sleep deprivation.

The present study aimed to evaluate the effects of treatment with lithium (Li) and valproate (VPA) on behaviors and brain BDNF, NGF, NT-3, NT-4 and GDNF levels in mice submitted to paradoxical sleep deprivation (PSD), which induces an animal model of mania. Male C57BL/6J mice received an intraperitoneal (i.p.) injection of saline solution (NaCl 0.09%, 1 ml/kg), Li (47.3 mg/kg, 1 ml/kg) or VPA (200 mg/kg, 1 ml/kg) once a day for seven days. Animals were randomly distributed into six groups (n = 10 per group): (1) Control + Sal; (2) Control + Li; (3) Control + VPA; (4) PSD + Sal; (5) PSD + Li; or (6) PSD + VPA. Animals were submitted to 36 h of PSD, and then, they were submitted to the open field test. The frontal cortex and hippocampus were dissected from the brain. The manic-like behaviors in the mice were analyzed. Treatment with Li and VPA reversed the behavioral alterations induced by PSD. PSD decreased BDNF, NGF, and GDNF levels in the frontal cortex and hippocampus of mice. The administration of Li and VPA protected the brain against the damage induced by PSD. However, PSD and the administration of Li and VPA did not affect the levels of NT-3 and NT-4 in either brain structure evaluated. In conclusion, the PSD protocol induced manic-like behavior in rats and induced alterations in neurotrophic factor levels. It seems that neurotrophic factors and sleep are essential targets to treat BD.

Possible Garcinia cambogia-Induced Mania With Psychosis: A Case Report.

Garcinia cambogia is a Southeast Asian fruit becoming increasingly popular as a weight management supplement. Hydroxycitric acid (HCA) is the primary active ingredient which demonstrates serotonergic- and muscarinic-enhancing properties via inhibition of selective serotonin reuptake and acetylcholinesterase. We report a young adult female with no history of bipolar disorder who developed mania and psychosis approximately 1 week following initiation of G cambogia and the Cleanse and Detox™ dietary supplement manufactured by Apex Vitality Health. She presented with a predominantly expansive mood, psychomotor agitation, disorganized and pressured speech, flight of ideas, grandiosity, delusions, and auditory hallucinations. Following discontinuation of G cambogia and the initiation of lithium and quetiapine, the patient experienced rapid and progressive mood stabilization and was discharged after 8 days. Seven previous case reports associating (hypo)mania and/or psychosis with G cambogia consumption have been published. The chronology of mania and/or psychosis onset may appear between 1 and 8 weeks following initiation of G cambogia. Psychiatric symptoms have resolved with G cambogia discontinuation in some instances and may not require chronic pharmacotherapy. Our report should encourage further research and case reports regarding this adverse event and the reconciliation of complete herbal supplement use at clinic visits and hospital admissions.

A critical review of trials of transcranial direct current stimulation and trigeminal nerve stimulation for depression: the issue of treatment-emergent mania.

OBJECTIVE:: This study is a critical review analyzing occurrence of treatment-emergent mania (TEM) related to transcranial direct current stimulation (tDCS) and trigeminal nerve stimulation (TNS). METHOD:: We present a systematic review of the literature on TEM related to tDCS and TNS treatment for major depressive disorder (MDD), conducted in accordance with the recommendations from Cochrane Group and the PRISMA guidelines. RESULTS:: Our search identified few reported episodes of TEM in the literature. In fact, we found 11 trials focused on treatment of MDD (seven controlled trials of tDCS and four trials of TNS, three open label and one controlled). We highlight the need for safety assessment in clinical research settings to establish with precision and in larger samples the risks inherent to the technique under investigation. CONCLUSION:: Safety assessment is of fundamental importance in clinical research. TEM is a very important safety issue in MDD trials. Further and larger controlled trials will help to clarify both the safety and the clinical effects of combinations of pharmacotherapy and tDCS or TNS in daily clinical practice.

A critical review of trials of transcranial direct current stimulation and trigeminal nerve stimulation for depression: the issue of treatment-emergent mania / Revisão crítica da literatura de ensaios clínicos em estimulação transcraniana por corrente contínua e estimulação de nervo trigêmeo para depressão: o problema da mania tratamento-emergente

Abstract Objective: This study is a critical review analyzing occurrence of treatment-emergent mania (TEM) related to transcranial direct current stimulation (tDCS) and trigeminal nerve stimulation (TNS). Method: We present a systematic review of the literature on TEM related to tDCS and TNS treatment for major depressive disorder (MDD), conducted in accordance with the recommendations from Cochrane Group and the PRISMA guidelines. Results: Our search identified few reported episodes of TEM in the literature. In fact, we found 11 trials focused on treatment of MDD (seven controlled trials of tDCS and four trials of TNS, three open label and one controlled). We highlight the need for safety assessment in clinical research settings to establish with precision and in larger samples the risks inherent to the technique under investigation. Conclusion: Safety assessment is of fundamental importance in clinical research. TEM is a very important safety issue in MDD trials. Further and larger controlled trials will help to clarify both the safety and the clinical effects of combinations of pharmacotherapy and tDCS or TNS in daily clinical practice.

Resumo Objetivo: O presente estudo consiste em uma revisão e análise crítica da ocorrência de mania tratamento-emergente (TEM) relacionada a estimulação transcraniana por corrente contínua (ETCC) e estimulação do nervo trigêmeo (TNS). Método: Apresentamos uma revisão sistemática de literatura sobre TEM relacionada a ETCC e TNS no tratamento de transtorno depressivo maior (TDM), conduzida de acordo com as recomendações do Grupo Cochrane e protocolo PRISMA. Resultados: A pesquisa identificou poucos relatos de TEM na literatura. Na verdade, foram encontrados 11 ensaios clínicos com foco no tratamento de TDM (sete estudos controlados de ETCC e quatro de TNS, sendo três abertos e um controlado). Destacamos a necessidade de avaliações de segurança em pesquisas clínicas para se estabelecer com maior precisão e em amostras maiores os riscos inerentes à técnica sob investigação. Conclusão: Avaliação de segurança é fundamental na pesquisa clínica. A TEM é um efeito adverso importante no tratamento do TDM. Maiores ensaios clínicos controlados ajudarão a esclarecer os efeitos clínicos e a segurança da combinação de psicotrópicos e ETCC ou TNS.

Early specific cognitive-behavioural psychotherapy in subjects at high risk for bipolar disorders: study protocol for a randomised controlled trial.

BACKGROUND: Bipolar disorders (BD) are among the most severe mental disorders with first clinical signs and symptoms frequently appearing in adolescence and early adulthood. The long latency in clinical diagnosis (and subsequent adequate treatment) adversely affects the course of disease, effectiveness of interventions and health-related quality of life, and increases the economic burden of BD. Despite uncertainties about risk constellations and symptomatology in the early stages of potentially developing BD, many adolescents and young adults seek help, and most of them suffer substantially from symptoms already leading to impairments in psychosocial functioning in school, training, at work and in their social relationships. We aimed to identify subjects at risk of developing BD and investigate the efficacy and safety of early specific cognitive-behavioural psychotherapy (CBT) in this subpopulation. METHODS/DESIGN: EarlyCBT is a randomised controlled multi-centre clinical trial to evaluate the efficacy and safety of early specific CBT, including stress management and problem solving strategies, with elements of mindfulness-based therapy (MBT) versus unstructured group meetings for 14 weeks each and follow-up until week 78. Participants are recruited at seven university hospitals throughout Germany, which provide in- and outpatient care (including early recognition centres) for psychiatric patients. Subjects at high risk must be 15 to 30 years old and meet the combination of specified affective symptomatology, reduction of psychosocial functioning, and family history for (schizo)affective disorders. Primary efficacy endpoints are differences in psychosocial functioning and defined affective symptomatology at 14 weeks between groups. Secondary endpoints include the above mentioned endpoints at 7, 24, 52 and 78 weeks and the change within groups compared to baseline; perception of, reaction to and coping with stress; and conversion to full BD. DISCUSSION: To our knowledge, this is the first study to evaluate early specific CBT in subjects at high risk for BD. Structured diagnostic interviews are used to map the risk status and development of disease. With our study, the level of evidence for the treatment of those young patients will be significantly raised. TRIAL REGISTRATION: WHO International Clinical Trials Platform (ICTRP), identifier: DRKS00000444, date of registration: 16 June 2010.

Secondary mania in a patient with delayed anoxic encephalopathy after carbon monoxide intoxication caused by a suicide attempt.

We report herein a female patient presenting with delayed anoxic encephalopathy after carbon monoxide (CO) intoxication. Five months after she attempted suicide in her car using burning charcoal, she showed manic symptoms including aggressive behaviors, irritability, decreased total sleep time, increased energy and sexual interest, and hyperactivity, as well as illusions and visual hallucinations related to bugs, certain animals, monsters and her ex-husband. Fluid-attenuated inversion recovery and T2-weighted images in brain magnetic resonance imaging showed white-matter hyperintensity in the frontal lobe and periventricular area. Her manic symptoms and psychotic features improved following daily administration of valproate (600 mg) and olanzapine (10 mg). These observations indicate that clinicians should monitor for delayed neuropsychiatric symptoms in patients with CO intoxication.

Emotion perception abnormalities across sensory modalities in bipolar disorder with psychotic features and schizophrenia.

Emotion perception deficits are a well-established feature of schizophrenia (SZ). Individuals with SZ have difficulty labeling emotional stimuli across auditory, visual, and audio-visual modalities and also misattribute threat towards neutral stimuli. The relationship between a history of psychosis and similar abnormalities in bipolar disorder (BD) is less clear. The current study set out to examine emotion perception across sensory modalities in a sample of 24 stabilized individuals meeting criteria for SZ, 24 remitted individuals meeting criteria for BD with psychotic features, 24 remitted individuals meeting criteria for BD without psychotic features, and 24 healthy controls. Results indicated that the bipolar with psychotic features group had intermediary performance between the SZ group and the other two groups for auditory, visual, and audio-visual items, with particularly poor performance in identifying angry stimuli. The SZ group misattributed neutral stimuli as negative when they were in visual format, but as positive when they were in auditory or audio-visual formats. The bipolar with psychotic features group had a trend towards misattributing more neutral visual stimuli as negative. These findings indicate that emotion perception deficits are present in BD with psychotic features and comparatively spared in BD without psychotic features, and that a similar bias of misattributing negative emotions to neutral visual stimuli may be present across diagnostic boundaries.

[Late-onset bipolar disorder following right thalamic injury]. / Trastorno bipolar de inicio tardío secundario a lesión talámica derecha.

Bipolar disorder occurs in the elderly ages and is frequently associated to a brain injury -cerebrovascular disease. Its diagnosis is based on the finding of an ischemic injury in specific regions of the brain. The case of a 63-year-old male with cardiovascular risk factors, who was admitted due to maniform picture during a two-year long bipolar affective syndrome is presented. The neuroimaging tests showed lacunar infarction in the right thalamus and diffuse foci of ischemia in subcortical white matter having right predominance. Due to the refractoriness to psychodrugs of an endogenomorphic depressive episode, electroconvulsive therapy was prescribed, with normalization of motor component, although without mood stabilization. The therapeutic strategies and the evolution of this form of bipolarity are discussed.

Some new food for thought: the role of vitamin D in the mental health of older adults.

Vitamin D, a multipurpose steroid hormone vital to health, has been increasingly implicated in the pathology of cognition and mental illness. Hypovitaminosis D is prevalent among older adults, and several studies suggest an association between hypovitaminosis D and basic and executive cognitive functions, depression, bipolar disorder, and schizophrenia. Vitamin D activates receptors on neurons in regions implicated in the regulation of behavior, stimulates neurotrophin release, and protects the brain by buffering antioxidant and anti-inflammatory defenses against vascular injury and improving metabolic and cardiovascular function. Although additional studies are needed to examine the impact of supplementation on cognition and mood disorders, given the known health benefits of vitamin D, we recommend greater supplementation in older adults.

Psychiatric symptoms following surgery for Parkinson's disease with an emphasis on subthalamic stimulation.

Bilateral subthalamic stimulation is a very effective neurosurgical treatment for advanced Parkinson's disease. Despite the range and frequency of psychiatric symptoms occurring in the postoperative state, most of these symptoms are transient and manageable. In clinical practice, preoperative psychiatric vulnerability, as with that of preoperative cognitive status, takes on an important role. Psychiatric assessment and active preoperative and postoperative intervention can potentially modify psychiatric outcomes. These psychiatric and psychological issues will take on greater importance, particularly with the rapid expansion of the number of neurosurgical sites and the need for adequate assessment and optimal management of patients. The paucity of the literature underscores the need for well-designed studies on psychiatric issues investigating both pathophysiology and clinical outcomes.

Circadian phase shifting, alerting, and antidepressant effects of bright light treatment.

Bright light treatment is the most potent melatonin suppressor and circadian phase shifter and is a safe nonpharmacologic antidepressant for seasonal depression. In addition, bright light treatment may restore performance in conditions of sleep debt and misalignment between peak performance and the athletic event. This article discusses the therapeutic use of bright light treatment, its side effects, and mechanisms of action.

[Manipulation of mental competence: an ethical problem in case of electrical stimulation of the subthalamic nucleus for severe Parkinson's disease]. / Manipuleerbare wilsbekwaamheid: een ethisch probleem bij elektrostimulatie van de nucleus subthalamicus voor ernstige ziekte van Parkinson.

Three years after the implantation of electrodes in the subthalamic nucleus (STN) and the start of deep brain stimulation (DBS) for advanced Parkinson's disease, a 62-year-old man was admitted because of a stimulation-related manic state that did not respond to treatment with a mood stabiliser and that led to chaotic behaviour, megalomania, serious financial debts and mental incompetence. Although adjustment of the stimulation parameters resulted in a normophoric state with a return of insight and capacity to judge, this was only at the cost of a serious exacerbation of his motor symptoms that left the patient bedridden. There was no therapeutic margin between the two states. Ultimately, there seemed to be only two alternatives: to admit the patient to a nursing home because of serious invalidity, but mentally in good condition, or to admit the patient to a chronic psychiatric ward because of a manic state, but with acceptable motor capacity and ADL functions. Thorough ethical evaluation followed. When not being stimulated, the patient was considered competent to decide about his own treatment; in this condition the patient chose for the second option. In accordance with his own wishes he was therefore legally committed to a chronic ward in the regional psychiatric hospital. The current ethical views on mental competence do not consider the potential influence of modern methods of treatment such as STN-DBS on this capacity.

Psychiatric complications of deep brain stimulation for Parkinson's disease.

BACKGROUND: The purpose of this article is to review the current literature regarding deep brain stimulation (DBS) of the subthalamic nucleus as a treatment for Parkinson's disease and to bring to the attention of the psychiatric community the possible psychiatric complications of this treatment. METHOD: A MEDLINE search of English-language publications was conducted using PubMed in July 2003. The search term used was deep brain stimulation. In addition, pertinent references were obtained from the retrieved articles. Reports and studies of psychiatric complications of DBS patients were reviewed and are discussed. A case report is presented of a man who developed hypomanic symptoms shortly after beginning DBS treatment for Parkinson's disease. RESULTS: There have been an increasing number of reports of postprocedure psychiatric complications, including depression, mania, aggression, and deficits in language. Improvement in symptoms of severe obsessive-compulsive disorder and depression has also been reported. CONCLUSION: As information continues to emerge, psychiatrists will play vital roles in the assessment and continuing care of patients who receive DBS. These findings may also provide the framework to determine which patients are at psychiatric risk from DBS. Symptoms of refractory obsessive-compulsive disorder have been noted to improve with DBS, which has led researchers to begin studying its effectiveness for this condition.