Psychological Science: Schizophrenia

Mycobacterium vaccae

Согласно результатам исследования, представленным на прошедшем в мае 2010 г. 110 съезде Американского общества по микробиологии (Сан-Диего, Калифорния), контакт с определёнными видами бактерий, присутствующими в окружающей среде, может приводить к улучшению настроения и повышению способности к обучению.

Группа исследователей под руководством D. Matthews занималась изучением Mycobacterium vaccae — микобактерии, которая в естественных условиях обитает в почве и может попадать в организм человека через пищеварительный тракт или дыхательные пути при нахождении на природе.

Могут ли бактерии сделать нас умнее?

Генотипы CYP450 и эффекты антипсихотиков

Metabolism of most antipsychotics depends on the CYP450 enzyme system, which is expressed predominantly in the liver (Table 1). CYP2D6 is one of these enzymes and may be responsible for metabolizing approximately 20% to 50% of all medications, including a number of antipsychotics.2 Genetic variations of CYP2D6 are common and the frequencies of these variants differ among racial groups.3

The half-life and other pharmacokinetic parameters of an antipsychotic metabolized by CYP2D6 may differ based on whether someone is a poor metabolizer (PM), intermediate metabolizer (IM), extensive metabolizer (EM), or ultrarapid metabolizer (UM).4 Regarding CYP2D6 metabolism among Whites, 3% to 5% are UMs, 70% to 80% are EMs, 10% to 17% are IMs, and 5% to 10% are PMs.5 By contrast, the percentage of PMs and UMs in the Asian population is low—about 1% for each phenotype; the IM phenotype is more common (65% to 70% in the Chinese population).5,6 The percentage of PMs in African Americans is roughly 2% to 6%.2

Cytochrome P450 (CYP) metabolism of commonly used antipsychotics*

Drug	CYP1A2	CYP2C9	CYP2C19	CYP2D6	CYP3A4/5
Aripiprazole				X	X
Asenapine	X			X	X
Chlorpromazine	X			X	X
Clozapine	X	X	X	X	X
Fluphenazine				X
Haloperidol	X			X	X
Iloperidone				X	X
Olanzapine	X			X
Paliperidone				X†	X†
Perphenazine	X	X	X	X	X
Quetiapine				X	X
Risperidone				X	X
Thioridazine			X	X
Ziprasidone	X				X
*Information obtained from the most recent prescribing information available from each drug’s manufacturer †According to paliperidone’s prescribing information, in vitro studies identify that CYP2D6 and CYP3A4 may be involved in paliperidone metabolism, but in vivo studies indicate that their role in eliminating paliperidone is minimal

Figure: Effects of CYP2D6 poor metabolizer status on the half-life of risperidone, aripiprazole, and iloperidone

EM: extensive metabolizer; PM: poor metabolizer
Source: References 7-9

It is not known if obtaining genotype information will provide better outcomes than a ‘trial and error’ approach

Should you order genetic testing to identify how patients metabolize antipsychotics?

Биомаркеры злоупотребления алкоголем

‘I’m sober, Doctor, really’: Best biomarkers for underreported alcohol use

Нелекарственные методы лечения инсомнии

Stimulus control therapy. Bootzin et al5 first evaluated stimulus control therapy for conditioned insomnia (subsequently identified as primary insomnia). This therapy’s goal is to interrupt the conditioned activation that occurs at bedtime. Patients are instructed to:

*

go to bed when sleepy
*

remain in bed for no more than 10 minutes (20 minutes if elderly) without sleeping
*

if unable to sleep, get up, do something boring, and return to bed only when sleepy
*

repeat getting up and returning as frequently as necessary until sleep onset.

For the first 2 weeks of stimulus control therapy, patients are required to self-monitor their sleep behaviors using a sleep diary. Stimulus control therapy is beneficial for primary insomnia and insomnia related to anxious preoccupation. About 70% of patients with conditioned insomnia will improve using stimulus control therapy,4 but it is not clear whether the primary effective intervention is:

*

patients dissociating conditioned responses at bedtime, or
*

the inevitable sleep restriction caused by getting out of bed.

Relaxation training. Progressive muscle relaxation is a common behavioral treatment of insomnia. Patients learn to tense and then relax individual muscles, beginning at the feet or head and working their way up or down the body. Patients are taught the difference between tension and relaxation to facilitate a relaxation response at bedtime. Another method is the body scanning technique, in which the patient “talks” to each body part, telling it to “relax… relax… relax.”

Relaxation training is predicated on the belief that insomnia is caused by somatized tension and psychophysiologic arousal. The greatest challenge to effective relaxation training is that patients need extensive daytime practice before they can bring the method to the bedroom.

Remind patients that “practice makes perfect.” Therapists often instruct patients to start practicing their relaxation method during the day while self-monitoring by sleep diary and restricting time in bed at night.2

CBTi is the most extensively investigated nonpharmacologic therapy for insomnia.6 It has been used to effectively manage comorbid insomnia in patients with psychiatric disorders,7,8 such as depression,9 generalized anxiety,10 and alcohol dependence,11 as well as those with breast cancer,12 traumatic brain injury,13 and fibromyalgia.14 Age does not appear to be a limitation; research trials show the technique is effective in elderly patients.15

CBTi incorporates cognitive strategies and behavioral interventions to improve sleep quality. Patient self-monitoring with sleep diaries and worksheets is essential.

CBTi commonly is provided in 5 to 8 sessions over 8 to 12 weeks, although studies have described abbreviated practices that used 2 sessions16 and CBTi delivered over the Internet.17 Highly trained clinical psychologists are at the forefront of therapy, but counselors and nurses in primary care settings have administered CBTi.18 For primary insomnia, CBTi is superior in efficacy to pharmacotherapy:

*

as initial treatment19
*

for long-term management4
*

in assisting discontinuation of hypnotic medication.20

Put your patients to sleep: Useful nondrug strategies for chronic insomnia

Вакцина от кокаиновой зависимости

Cocaine is a very simple molecule, but you can attach a simple molecule to a complex molecule and still trigger the immune system. You can use this method to develop antibodies to cocaine. When an individual uses cocaine, the antibodies will bind to the cocaine in the blood stream and the drug never reaches the brain because the molecule is now too large to pass the blood-brain barrier.

Pharmacotherapy for cocaine dependence: Most evidence is weak

Study	Design	Results
Disulfiram
Pani et al, 20108	Meta-analysis of 7 studies with 492 cocaine-dependent patients	Researchers found ‘low evidence’ supporting disulfiram for treating cocaine dependence
Modafinil
Dackis et al, 20059	62 cocaine-dependent patients randomized to modafinil, 400 mg/d, or placebo for 8 weeks	Patients receiving modafinil provided significantly more BE-negative urine samples and were significantly more likely to achieve ≥3 weeks of cocaine abstinence
Anderson et al, 200910	210 cocaine-dependent patients randomized to modafinil, 200 mg/d or 400 mg/d, or placebo for 12 weeks	Modafinil significantly reduced cocaine craving but did not significantly improve the average weekly percentage of cocaine non-use days
Tiagabine
Winhusen et al, 200711	141 cocaine-dependent patients randomized to tiagabine, 20 mg/d, or placebo for 12 weeks	No significant changes in cocaine use vs placebo as measured by self-report and urine BE
Baclofen
Kahn et al, 200912	Cocaine-dependent patients randomized to baclofen, 60 mg/d, or placebo for 8 weeks	No significant difference between groups in cocaine use as measured by urine BE
Ondansetron
Johnson et al, 200613	63 cocaine-dependent patients randomized to ondansetron, 0.25 mg, 1 mg, or 4 mg twice daily, or placebo for 10 weeks	The odansetron 4 mg group had a significantly greater rate of improvement in percentage of patients with a cocaine-free week compared with the placebo group
BE: benzoylecgonine

Vaccine for cocaine addiction: A promising new immunotherapy

Рекомендации по лечению инсомнии и других расстройств сна

Recommendations for Diagnosis and Treatment

Specific evidence-based recommendations for diagnosis and treatment of insomnia and other sleep disorders, and their accompanying level of evidence rating, are as follows:

* The diagnosis of insomnia is primarily based on complaints provided in the clinical interview by the patient, family, and/or caregiver, ideally corroborated by a patient diary (level of evidence, A).
* Referral to a specialist sleep center may be indicated for other tests in some cases, such as actigraphy for differential diagnosis of circadian rhythm disorder (level of evidence, A), polysomnography for suspected parasomnia or other primary sleep disorder (level of evidence, A), or in the case of treatment failure (level of evidence, D).
* Insomnia should be treated because it impairs quality of life and many areas of functioning and is associated with an increased risk for depression, anxiety, and possibly cardiovascular disorders (level of evidence, A). Treatment goals are to reduce distress and to improve daytime function. Choice of treatment modality is based on the particular pattern of problem, such as sleep-onset insomnia or sleep maintenance, as well as on the evidence supporting use of specific treatments.
* For chronic insomnia, cognitive behavioral therapy (CBT)-based treatment packages are effective and should be offered to patients as a first-line treatment (level of evidence, A). CBT, which may include sleep restriction and stimulus control, should be made available in more settings.
* When prescribing hypnotic drug treatment, clinicians need to consider efficacy, safety, and duration of action (level of evidence, A). Other issues to consider may include previous efficacy or adverse effects of the drug and history of substance abuse or dependence (level of evidence, D).
* Recommendations for long-term hypnotic drug treatment are to use it as clinically indicated (level of evidence, A). To discontinue long-term hypnotic drug therapy, intermittent use should first be attempted if feasible. Depending on ongoing life circumstances and patient consent, discontinuation should be attempted every 3 to 6 months or at regular intervals (level of evidence, D). During taper of long-term hypnotic drug treatment, CBT improves outcome (level of evidence, A).
* When using antidepressants, clinicians should apply their knowledge of pharmacology (level of evidence, A). When there is a comorbid mood disorder, antidepressants should be used at therapeutic doses (level of evidence, A). However, clinicians should beware that overdose of tricyclic antidepressants can be toxic even when low-unit doses are prescribed (level of evidence, A).
* Because of frequent adverse effects of antipsychotic drugs, as well as a few reports of abuse, there is no indication for use as first-line treatment of insomnia or other sleep disorders (level of evidence, D).
* Antihistamines have a limited role in psychiatric and primary care practice for the management of insomnia (level of evidence, D).

New Guidelines Issued for Insomnia and Other Sleep Disorders

Шизофрения у пожилых

Lowering the anticholinergic load is a key component of treating older schizophrenia patients

Schizophrenia in older adults

Исследование SAM-e при депресии

A total of 73 adults were enrolled in this six-week study and randomly assigned to the placebo control group or the SAM-e treatment group.

SAM-e, in combination with standard depression treatment, was more effective than antidepressant treatment alone in improving measures of depression and remission rates of patients with significant clinical depression. SAM-e-treated subjects had a greater response and remission rate to treatment than the placebo-treated group. SAM-e was well-tolerated with no reported adverse reactions.

Dietary Supplement SAM-e Aids Treatment of Depression

Механизм антидепрессивного действия кетамина

The Mechanism Behind Fast-Acting Antidepressant Ketamine

Самоповреждения, эмоции, brain imaging

Why Self-Harm Feels Good in the Brain

Эффективность антидепрессантов в лечении негативной симптоматики при шизофрении

Background

Treatment of negative symptoms in chronic schizophrenia continues to be a major clinical issue.

Aims

To analyse the efficacy of add-on antidepressants for the treatment of negative symptoms of chronic schizophrenia.

Method

Systematic review and meta-analysis of randomised controlled trials comparing the effect of antidepressants and placebo on the negative symptoms of chronic schizophrenia, measured through standardised rating scales. Outcome was measured as standardised mean difference between end-of-trial and baseline scores of negative symptoms.

Results

There were 23 trials from 22 publications (n = 819). The antidepressants involved were selective serotonin reuptake inhibitors, mirtazapine, reboxetine, mianserin, trazodone and ritanserin; trials on other antidepressants were not available. The overall standardised mean difference was moderate (–0.48) in favour of antidepressants and subgroup analysis revealed significant responses for fluoxetine, trazodone and ritanserin.

Conclusions

Antidepressants along with antipsychotics are more effective in treating the negative symptoms of schizophrenia than antipsychotics alone.

Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis

Семейная история тревожных и депрессивных расстройств и утренний уровень кортизола

Background

It is unclear whether altered hypothalamic–pituitary–adrenal (HPA) axis regulation, which frequently accompanies depression and anxiety disorders, represents a trait rather than a state factor.

Aims

To examine whether HPA axis dysregulation represents a biological vulnerability for these disorders, we compared cortisol levels in unaffected people with and without a parental history of depressive or anxiety disorders. We additionally examined whether possible HPA axis dysregulations resemble those observed in participants with depression or anxiety disorders.

Method

Data were from the Netherlands Study of Depression and Anxiety. Within the participants without a lifetime diagnoses of depression or anxiety disorders, three groups were distinguished: 180 people without parental history, 114 with self-reported parental history and 74 with CIDI-diagnosed parental history. These groups were additionally compared with people with major depressive disorder or panic disorder with agoraphobia (n = 1262). Salivary cortisol samples were obtained upon awakening, and 30, 45 and 60 min later.

Results

As compared with unaffected participants without parental history, unaffected individuals with diagnosed parental history of depression or anxiety showed a significantly higher cortisol awakening curve (effect size (d) = 0.50), which was similar to that observed in the participants with depression or anxiety disorders. Unaffected people with self-reported parental history did not differ in awakening cortisol levels from unaffected people without parental history.

Conclusions

Unaffected individuals with parental history of depression or anxiety showed a higher cortisol awakening curve, similar to that of the participants with depression or anxiety disorders. This suggests that a higher cortisol awakening curve reflects a trait marker, indicating an underlying biological vulnerability for the development of depressive and anxiety disorders.
Parental history of depression or anxiety and the cortisol awakening response

Пернициозная анемия в форме кататонии без признаков анемии и макроцитоза

Pernicious anaemia can present with psychiatric symptoms before haematological or neurological manifestations appear. We describe a young woman who presented with insidious onset catatonia without evidence of psychosis or depression. Blood count and mean cell volume were normal and neurological findings were equivocal. Low B12 levels and intrinsic factor antibodies were found only by chance when they were included in a battery of further investigations. B12 replacement was followed by prompt improvement. This case provides an argument for wider screening for B12 deficiency in certain individuals with psychiatric disorders.

Pernicious anaemia presenting as catatonia without signs of anaemia or macrocytosis

Болезнь Паркинсона, иммунная система, воспаление

The team confirmed that a gene in the human leukocyte antigen (HLA) region was strongly linked with Parkinson’s disease; this region contains a large number of genes related to immune system function...
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen are protective against Parkinson’s disease, according to the study.

However, not everyone benefits from them to the same degree. The amount of risk reduction conferred by NSAIDs may vary widely depending on genetic differences, say the researchers.

Investigating the connection between Parkinson’s disease and inflammation, especially in the context of the variable genetic makeups of individuals, likely would lead to better, more selective medicines for treatment.

Parkinson’s May Be Linked to Immune System