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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Alcoholism is a chronic relapsing disorder characterized by compulsive drinking, alcohol seeking, loss of control over alcohol consumption, and impaired social and occupational functioning. Treatment of Alcohol Dependence (AD) comprises two steps, detoxification and relapse prevention (RP). Traditionally, long half-life benzodiazepines have been the most widely used agents for alcohol detoxification. On the other hand, disulfiram, naltrexone and acamprosate are the three drugs that have been approved for relapse prevention. In the last decades, nevertheless, there is a growing interest in the use of anticonvulsant drugs in the management of both, detoxification and relapse prevention of alcohol.
To review the different pharmacological strategies in which an anticonvulsant was used in the management of AD.
We searched in MEDLINE and in the Cochrane Database System Review, selecting all studies from 1980 until present, in which a pharmacological intervention with anticonvulsant agents was made for alcohol detoxification or RP.
The most tested anticonvulsant drugs are the classical Carbamazepine and Valproate. Both have demonstrated to be efficacious in Alcohol Withdrawal Syndrome and RP. However, the use of these agents has been limited by their hepatic and hematologic toxicity. Novel anticonvulsants such as Gabapentin, Pregabalin, Topiramate, Oxcarbazepine and Zonisamide have also been found to be effective, with the advantage of rapid onset of action, lower toxicity and fewer side effects.
Anticonvulsants are efficacious and safe agents in the management of AD. Further randomized, double-blind, placebo-controlled trials are warranted to increase the evidence of the use of these agents.
Electroconvulsive Therapy (ECT) is a safe and effective technique widely used in our area. Scientific literature related to the application of this technique is continuously developing, specifically with regard to the placement of the electrodes, the amplitude of the stimulus pulse administered, the initial charge used, and the anesthetic agent involved.
The primary aim of this study was to analyze technical variables associated with the use of ECT in our hospital, and compare them to the guidelines of the protocol developed in our hospital and international standards.
We performed a review of Clinical Histories of the patients that were treated with ECT in the “Hospital 12 de Octubre” (Madrid, Spain), in the period comprised between January 1st, 2008 and December 31st, 2009. We collected data related to the application of the technique, socio-demographic variables and clinical profiles. We used descriptive statistics to analyze our data.
During this period, 602 ECT sessions were applied. Placement of the electrodes was unilateral in 58% of subjects with Affective Disorders and 8% of subjects with Schizophrenia. The amplitude of the stimulus pulse was 1 ms. Mean charge administered in the initial and final session was 236.85 mC and 357.16 mC, respectively. Etomidate was used as anesthetic in 68% of cases.
ECT technical variables applied in our hospital are adjusted to guidelines of our area and international recommendations. Longitudinal studies are warranted in order to objectively assess techinical variables associated to ECT.
Varicella Zoster Virus infection is quite a common condition overseas, for which Acyclovir seems to specifically help reducing the duration and severity of its symptoms.
Some central nervous system side-effects have been described while receiving treatment with Acyclovir or one of its analogs Ganciclovir and Valacyclovir, and eventually psychiatric disturbances between them.
We report the case of an Acyclovir-induced psychosis with manic symptoms in a 22 years-old woman with no previous psychiatric history.
The patient presented with irritable mood and grandiose delusions 72 hours after starting oral Acyclovir for a chickenpox infection coursing with diseminated rash.
The patient was admitted to the psychiatric unit 2 weeks after stopping treatment, albeit symptoms persisted. She was treated with Olanzapine in first place with modest improvement and Haloperidol in second place, finally recovering her previous mental state with no residual symptoms.
There is a significant body of evidence warning about neuropsychiatric disturbances as a side-effect of treatment with Acyclovir and its analogs, specially when using intravenous administration, or in a renal failure condition. Although uncommon, psychosis with manic symptoms in young and healthy patients should be kept in mind in order to recognise it and offer best support.
Disturbed eating behaviors are a significant health concern among child and adolescents with type 1 diabetes mellitus (DM1) and are generally related to poor glycemic control, ketoacidosis, hospitalization and microvascular complications. Rates of eating problems among youths with DM1 have been reported to be as high as 38%.
To review clinical characteristics, demographic profiles and risk factors for the development of eating disturbances among child and adolescents with DM1.
We performed a literature research of articles from 1980 until present, in which a Disturbed Eating Behavior appeared comorbid with DM1 in children and adolescents, using Medline database.
Almost all studies selected report a high prevalence of eating disturbances of child and adolescents with DM1 when compared with healthy pairs. This population trend to develop body image discontent and lower self-esteem. They are more likely to diet, skip meals, and omit insulin. All these practices have been associated with worsening diabetic medical complications and poorer psychological outcome.
Due to the high prevalence and severe medical and psychological complications associated with disturbed eating behaviors among pediatric population with DM1, clinicians and school professionals may benefit from specialized training to identify the range of unhealthy weight control behaviors used by youths with DM1. Preventive programs that address disturbed eating behaviors should be provided for adolescents with DM1 in order to reduce the psychological and medical impact of this comorbid situation.
Childhood or Early Onset Schizophrenia (EOS), defined as the onset of psychotic symptoms before the thirteenth birthday, represents a rare, clinically severe variant, associated with significant chronic functional impairment and poor response to antipsychotic treatment. Despite of that, in clinical practice, atypical agents have become the treatment of choice in patients with EOS.
To review the different pharmacological strategies, in which an atypical antipsychotic was used in the management of EOS in childhood and adolescence.
We conducted a literature search of articles related to the use of atypical antipsychotics in children and adolescents with EOS in the last 20 years from the Medline database.
Several atypical antipsychotics, such as Risperidone, Olanzapine, Quetiapine, Aripiprazol and Clozapine were consistently found to reduce the severity of psychotic symptoms in EOS when compared to placebo. Although Clozapine has demonstrated to be more efficacious than other atypical and typical antipsychotics, it remains the medication of last resort due to its profile of side effects. Finally, in general, children and adolescent have a higher risk of extrapyramidal symptoms, akathisia, prolactin elevation, sedation and metabolic effects of atypical antipsychotics than adults.
Antipsychotics are the mainstay of treatment of EOS. Randomized controlled trials suggest a trend to superior efficacy for atypical antipsychotics over classic antipsychotic. Children and adolescents trend to be more sensible to antipsychotic side effects. Clinicians should be aware of this problem and be careful when monitoring this type of treatment.
It is well known that impulsivity and stress are risk factors for the development of addictive disorders, and more specifically alcohol dependence. Impulsivity has two dimensions: behavioural inhibition and delay of reward. The Fear- Conditioning paradigm of the Startle response (SR), which refers to the potentiation of the startle amplitude after the exposure to aversive stimulus, can be used as a stress test. The aim of this study was to explore the correlation between impulsivity laboratory tasks and the Fear-Conditioning (FC) paradigm of the SR as risk factors for the development of alcohol dependence.
The sample included 40 abstinent alcoholic men, who met DSM-IV criteria for Alcohol Dependence and had been abstinent for at least one month. Impulsivity was assessed using two laboratory tests: Stop-Signal Task (SST) and Differential Reinforcement for Low-Rate Responding (DRL6). The FC paradigm of the SR was used as a stress test. Patients were compared to 40 matched controls.
We found a positive correlation between SST tasks and the FC paradigm of the SR (p < 0,05) and a negative correlation between the DRL6 tasks and the FC paradigm of the SR (p < 0,05) in the patient's group. This significant correlation was not found in controls.
Impulsivity and stress are significantly correlated in alcohol dependent patients. This means that while healthy subjects cope with stress, alcohol dependent patients react with higher impulsivity when they are exposed to stress situations and this could lead them to drink alcohol to relieve anxiety and depressive symptoms.
Abrupt discontinuation of antidepressants, especially Selective Serotonin Reuptake Inhibitors (SSRI) and Dual-Action Antidepressants such as Venlafaxine, can lead to several psychological and somatic symptoms, which includes restlessness, psychomotor agitation, nervousness, anxiety, crying spells, irritability, depersonalization, decreased mood, memory disturbances, decreased concentration, and/or slowed thinking, nausea, dizziness and headache. Additionally, it has been demonstrated that sudden discontinuation of antiepileptic drugs in free-seizure patients, can increase the risk of suffering a seizure episode.
The aim of this study was to review the discontinuation syndrome associated with antidepressants and antiepileptic drugs, it's pharmacological management and strategies to prevent it.
We searched in MEDLINE selecting all the studies from 1990 until the present, related with the discontinuation of antidepressants and anticonvulsants. All kind of studies and reported cases are included. We also describe the case of a 47 year old patient, diagnosed with Obsessive Compulsive Disorder (OCD), who developed delirium and two seizure episodes after sudden cessation of his treatment with Venlafaxine 225 mg/ day and Pregabaline 225 mg/ day.
Withdrawal symptoms are common during discontinuation of antidepressants, especially in the case of SSRI and Venlafaxine. They are more frequently associated with their prolonged use and with agents with a short half-life. These symptoms are usually mild and transient. However, there are several cases reported in the literature describing the occurrence of delirium as a result of abrupt discontinuation of antidepressants. Additionally, it has also been reported that stopping antiepileptic drugs in seizure-free patients can increase the risk of developing a seizure episode.
Withdrawal Syndrome associated to the discontinuation of antidepressants and antiepileptic drugs is well established. Psychiatrists and General Practitioners should be aware of possible withdrawal symptoms when interrupting these treatments. Management strategies include gradual tapering of doses, clinical monitoring and patient education.
An under-recognized life-threatening adverse effect of clozapine is the gastrointestinal hypomotility. It represents a serious problem. Clozapine is an atypical antipsychotic which commonly produces ileus. The risk is higher when we associate clozapine to drugs, such us anticholinergic and tricyclic. Ileus can produce the death in our patients, therefore we will check constipation in our daily clinical practice as a measure to avoid these side effectS.
We looked through Medline for articles published since 2005 regarding Clozapine and Ileus. We will present the case of a patient who developed Ileus as the side effect of clozapine.
Constipation is very common in patients with schizophrenia (until 50%). Risk factors developing ileus in psychotic patients are: women, age, anticholinergic drugs, first generation of antipsychotics, clozapine, opioids and tricyclic antidepressants. Taking into account that this side effect can be mortal some recommendations that can reduce gastrointestinal hipomotility in this population are: a high fiber diet, exercise and the use of a softening laxative. In the case a patient treated with clozapine suffers from ileus we should shift the clozapine to aripiprazole or Amisulpride treatment. Moreover, we can use prokinetic drugs and surgery in the most complicated cases. Then, clozapine can be introduced after the ileus problem has been solved.
1 Gastrointestinal hypomotility has a high prevalence in psychotic treatments. 2 Avoiding the use of other drugs that produce constipation. 3 Offer advice to avoid the constipation. 4 If ileus is present, stop the clozapine treatment and shift it to aripiprazole or Amisulpride.
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