изотретионин, депрессии, суицид, акне

"Isotretinoin (13-cis-retinoic acid) has been used since the 1980s to treat severe recalcitrant nodular acne with good effect, but case reports and spontaneous reporting of adverse drug reactions have suggested an association between isotretinoin, depression, and suicidal behaviour," write Anders Sundström, from the Karolinska Institute in Stockholm, Sweden, and colleagues. "Observational studies have had conflicting results, however."

Severe acne is associated with the risk for suicide attempt even before treatment with isotretinoin was started, although the risk is increased during treatment and up to 6 months afterward, according to the results of a retrospective Swedish cohort study reported online first November 12 in the BMJ.

Severe Acne Linked to Suicide Risk Even Before Treatment Is Started

Раннее вмешательство при высоком риске психоза

Antipsychotics and cognitive therapy don't appear to help youth at ultra high risk for psychosis, according to an interim analysis of a small randomized trial.

But the study was underpowered, and it's still unclear whether early intervention can help prevent full-blown psychotic disorders in youth with putative prodromal symptoms, according to Dr. Alison R. Yung, of Orygen Research Center and the University of Melbourne in Victoria, Australia, and colleagues.

At 6 Months, Unclear If Early Intervention for Psychosis Works

Механиз атипичного действия антипсихотиков, fast off

Background: Although the principal brain target that all antipsychotic drugs attach to is the dopamine D2 receptor, traditional or typical antipsychotics, by attaching to it, induce extrapyramidal signs and symptoms (EPS). They also, by binding to the D2 receptor, elevate serum prolactin. Atypical antipsychotics given in dosages within the clinically effective range do not bring about these adverse clinical effects. To understand how these drugs work, it is important to examine the atypical antipsychotics’ mechanism of action and how it differs from that of the more typical drugs. Method: This review analyzes the affinities, the occupancies, and the dissociation time-course of various antipsychotics at dopamine D2 receptors and at serotonin (5-HT) receptors, both in the test tube and in live patients. Results: Of the 31 antipsychotics examined, the older traditional antipsychotics such as trifluperazine, pimozide, chlorpromazine, fluphenazine, haloperidol, and flupenthixol bind more tightly than dopamine itself to the dopamine D2 receptor, with dissociation constants that are lower than that for dopamine. The newer, atypical antipsychotics such as quetiapine, remoxipride, clozapine, olanzapine, sertindole, ziprasidone, and amisulpride all bind more loosely than dopamine to the dopamine D2 receptor and have dissociation constants higher than that for dopamine. These tight and loose binding data agree with the rates of antipsychotic dissociation from the human-cloned D2 receptor. For instance, radioactive haloperidol, chlorpromazine, and raclopride all dissociate very slowly over a 30-minute time span, while radioactive quetiapine, clozapine, remoxipride, and amisulpride dissociate rapidly, in less than 60 seconds. These data also match clinical brain-imaging findings that show haloperidol remaining constantly bound to D2 in humans undergoing 2 positron emission tomography (PET) scans 24 hours apart. Conversely, the occupation of D2 by clozapine or quetiapine has mostly disappeared after 24 hours. Conclusion: Atypicals clinically help patients by transiently occupying D2 receptors and then rapidly dissociating to allow normal dopamine neurotransmission. This keeps prolactin levels normal, spares cognition, and obviates EPS. One theory of atypicality is that the newer drugs block 5-HT2A receptors at the same time as they block dopamine receptors and that, somehow, this serotonin-dopamine balance confers atypicality. This, however, is not borne out by the results. While 5-HT2A receptors are readily blocked at low dosages of most atypical antipsychotic drugs (with the important exceptions of remoxipride and amisulpride, neither of which is available for use in Canada) the dosages at which this happens are below those needed to alleviate psychosis. In fact, the antipsychotic threshold occupancy of D2 for antipsychotic action remains at about 65% for both typical and atypical antipsychotic drugs, regardless of whether 5-HT2A receptors are blocked or not. At the same time, the antipsychotic threshold occupancy of D2 for eliciting EPS remains at about 80% for both typical and atypical antipsychotics, regardless of the occupancy of 5-HT2A receptors. Relevance: The "fast-off-D2" theory, on the other hand, predicts which antipsychotic compounds will or will not produce EPS and hyperprolactinemia and which compounds present a relatively low risk for tardive dyskinesia. This theory also explains why L-dopa psychosis responds to low atypical antipsychotic dosages, and it suggests various individualized treatment strategies.

Atypical Antipsychotics: Mechanism of Action

Посмертные исследования больных шизофренией на токсоплазмоз и герпесвирусы

Herpes simplex virus (HSV), Epstein–Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus-6 (HHV-6) are viruses capable of establishing latency. All of these infect the CNS and have been detected in human postmortem brains. Toxoplasma gondii is a protozoan organism which can reactivate in the brains of previously infected immunocompromised individuals. To screen for the presence of herpesviruses and T. gondii in postmortem orbital frontal brain samples from patients with schizophrenia, affective disorders, and controls, we used nested-polymerase chain reaction (n-PCR)/sequencing. We identified HHV-6B sequences in 2/51 postmortem brain samples but no sequences from other herpesviruses. We did not detect sequences of T. gondii in the postmortem brains. Additional studies including ones directed at the sensitive detection of viral nucleic acids in multiple brain regions should be directed at confirming or excluding a role for viruses and protozoa in the etiology of these disorders.

Herpesviruses and Toxoplasma gondii in orbital frontal cortex of psychiatric patients

+ Antibodies to Toxoplasma gondii in Patients With Schizophrenia: A Meta-Analysis
+ Toxoplasmosis–Schizophrenia Research

Бупренорфин в терапии резистентной депрессии

Nonetheless, there has been little work published concerning the antidepressant effects of buprenorphine in treatment refractory depression in the absence of opiate dependence since my 1995 paper. I find only one report, by Nyhuis et al in 2008, looking at low-dose sublingual buprenorphine monotherapy in 6 extremely treatment refractory hospitalized patients with a very marked response to a maximum dose of 0.8 to 2.0 mg/d for a total of 7 days of open label treatment. All but one of these subjects experienced full remission acutely.

Q&A: Buprenorphine for Treatment Resistant Depression?

Сравнение атипичных антипсихотиков

For example, when switching from a tightly binding anticholinergic or antihistaminergic medication (eg, olanzapine, quetiapine, clozapine) to one with less anticholinergic or antihistaminergic affinity (eg, aripiprazole, risperidone, ziprasidone), often transient rebound anxiety, insomnia, agitation and restlessness can occur. In addition, when switching from a tighter D2 binding agent to a looser-binding agent (eg, from risperidone to clozapine or quetiapine) or, particularly, to a partial dopamine agonist (eg aripiprazole) dopamine rebound symptoms, such as often transient worsening of psychosis, mania or aggression/agitation, can occur. A pharmacokinetic dopamine rebound may also occur when switching from a short half-life antipsychotic to a longer half-life antipsychotic (Table 1).4

The abrupt switch has the greatest potential for rebound and withdrawal phenomena. Even the conventional cross-titration can lead to problems when the pre-switch antipsychotic has a shorter half life and/or blocks more tightly cholinergic, histaminergic or dopaminergic receptors than the post-switch antipsychotic. Rebound phenomena can be minimized by avoiding abrupt or fast switching when the pre- and post-switch receptor affinities and/or half-lives differ considerably. Instead, an overlapping or “plateau” switch should be used. This consists of decreasing the pre-switch antipsychotic slowly (eg, 25–50% every 5 half-lives) and only after the post-switch antipsychotic has reached steady state (ie, ≤5 half lives on target dose). Adding calming medications during the switch period, such as benzodiazepines, antihistamines or sleep aides, can also minimize rebound phenomena.

A number of non-antipsychotic augmentation strategies have also been tested in schizophrenia patients with insufficient response to antipsychotic monotherapy. Of these, lithium,16 carbamazepine,17 and beta blockers18 were not superior to placebo when added to an antipsychotic. Similarly, benzodiazepine19 and valproate augmentation20 also did not show long-term superiority compared to placebo, although both agents might speed up the initial response. Although two large-scale studies showed no superiority of lamotrigine augmentation of antipsychotics compared to placebo,21 a meta-analysis demonstrated significant superiority regarding global ratings of psychopathology, positive and negative symptom change, as well as study-defined response when outcomes of patients were combined in whom lamotrigine was added to clozapine.22 This, however, has not been verified in a prospective study.

ECT augmentation has also been shown to be superior, both for acute efficacy and in maintenance treatment, when added to antipsychotic monotherapy in patients who have failed antipsychotic monotherapy.23

One meta-analysis suggested that augmentation of antipsychotics with antidepressants may be more helpful than placebo for schizophrenia patients with predominantly negative symptoms.24 Larger, validating studies are needed, however, and specific effects on negative symptoms need to be distinguished from proven effects of antidepressants on depressive symptoms in schizophrenia patients.25

Practical Dosing Strategies in the Treatment of Schizophrenia: Part 2 - Switching and Combining Antipsychotics

Монотерапия рисперидоном в сравнении с терапией комбинацией низких доз рисперидона и галоперидола

Monotherapy is recommended for schizophrenia treatment, but the risk-benefit issue of antipsychotic drug combination (except for clozapine) remains unclear. Risperidone, an atypical antipsychotic drug, has a lower incidence of extrapyramidal syndrome but higher risks of prolactinemia and metabolic syndrome than haloperidol, a typical agent. This study compared efficacy and safety of risperidone monotherapy versus low-dose risperidone plus low-dose haloperidol in schizophrenia. In this 6-week, double-blind study, patients were randomized to the combination group (2-mg/d risperidone plus 2-mg/d haloperidol, n = 46) or the monotherapy group (4-mg/d risperidone, n = 42). Efficacy assessments included Clinical Global Impression-Severity, Positive and Negative Syndrome Scale and subscales, Calgary Depression Scale, Global Assessment of Functioning, and Medical Outcomes Study Short-Form 36. Safety was rigorously monitored. Response was defined as 30% reduction in the Positive and Negative Syndrome Scale total score. The 2 treatment groups were similar in (1) demographic and clinical characteristics at baseline, (2) response rate, and (3) improvement in various psychopathological measures and quality of life at end point. The monotherapy group had a higher increase in prolactin levels (P = 0.04) and Simpson-Angus Scale scores (P = 0.04) and a higher percentage of biperiden use (P = 0.045). There were no significant between-group difference in changes in weight, vital signs, corrected QT interval, liver/renal function, fasting glucose level, and lipid profiles. The findings suggest that risperidone monotherapy may yield higher prolactin levels than a combination of low-dose risperidone plus low-dose haloperidol. The 2 treatment groups are similar in efficacy, life quality, and other safety profiles. Future long-term studies are warranted.

A randomized, double-blind comparison of risperidone versus low-dose risperidone plus low-dose haloperidol in treating schizophrenia.

Потенциирование клозапина: сульпирид, амисульприд, ламотриджин

A frequent treatment strategy for clozapine-resistant patients with schizophrenia is the use of specific augmentors that are suitable for adjunctive therapy. Clozapine is a polyvalent drug but it lacks high-potency dopamine receptor blockade (Kerwin & Osborne, 2000). Therefore, there has been interest in using as augmentors substituted benzamides with highly selective dopamine receptor blocking profiles (Kerwin, 2000). Augmentation strategies incorporating sulpiride are well documented. The authors of one study of sulpiride augmentation in 28 patients partially responsive to clozapine (Shiloh et al, 1997) noted a mean reduction of about 40–50% in various clinical response scores (Brief Psychiatric Rating Scale and Scale for the Assessment of Positive Symptoms).

Several groups have been interested in mimicking this study with amisulpride, a relative of sulpiride that is even more selective at the dopamine D2 receptor. A case series by Zink et al(2004) showed improvement in previously treatment-resistant symptoms following a combined treatment strategy of clozapine and amisulpride. In addition, our group performed an open trial of amisulpride augmentation in a long-term (52 weeks) study. Significant improvement was observed in half of the patients, with no additional side-effects. Moreover, this study monitored plasma levels to determine whether this was a pharmacokinetic interaction. Clozapine levels did not change throughout the duration of the trial, suggesting a pharmacodynamic interaction (Munro et al, 2004).

Augmentation with anti-epileptics
A glutamate hyperfunction hypothesis of schizophrenia has generated interest in the role of glutamate release inhibitors as clozapine augmentors. In a study of 26 treatment-resistant patients receiving lamotrigine (17) or topirimate (9) in addition to their existing antipsychotic treatment (a variety of antipsychotics), a significant improvement was observed when lamotrigine was added to risperidone, haloperidol, olanzapine or flupenthixol. However, no significant effect was observed in patients receiving topirimate augmentation in addition to clozapine, olanzapine, haloperidol or flupenthixol (Dursun & Deakin, 2001). The therapeutic effects of lamotrigine augmentation were also assessed in a rigorous randomised placebo-controlled cross-over study of 34 clozapine-resistant patients (Tiihonen et al, 2003). In this 14-week study, lamotrigine treatment significantly improved positive symptoms and general psychopathological symptoms, but had no effect on negative symptoms. The authors suggested that this was the first time a non-dopamine antagonist had proven efficacy in schizophrenia, giving further credence to the hyperglutamate neurotransmission hypothesis for the generation of positive symptoms in the disorder.

Management of clozapine-resistant schizophrenia

Аутистическая симптоматика в результате вирусного поражения головного мозга

What happened to her? She suffered from herpes simplex encephalitis, a viral infection of the brain. X-rays at the age of 22 showed serious damage to the temporal lobes of the brain, extending to parts of the parietal lobes. (No pictures were provided, however.)

Can her case really be described as a "typical autistic syndrome"? Certainly, there are striking similarities, from the obsessive routines, to the echolalia (repeating what other people say), to the avoidance of eye contact, all classic symptoms of severe autism.

Of course it's always possible that the case report was written to accentuate these similarities, in order to make a nice publication. There have been a handful of other similar cases, though the same caveats apply. Still, if we do accept that these patients are indeed autistic, the implications for understanding the neurobiology of "normal" autism are obvious.

Autism Following Viral Infection

Баклофен при абстинентном синдроме

A small study in Minnesota has replicated findings from Italy indicating that off-label use of the gamma-aminobutyric acid–derivative baclofen is effective in treating symptoms of alcohol withdrawal syndrome (AWS). The drug has been approved for treating spasticity.

The prospective, double-blind, randomized, placebo-controlled study involved 79 inpatients at risk for AWS. Of these, 44 developed symptoms of AWS and were randomly assigned to receive baclofen 10 mg or placebo 3 times per day. In all, 31 patients completed the 72 hours of observation and assessment required by the study and were available for evaluation.

When the study was unblinded, the researchers found that 1/18 patients in the baclofen group and 7/13 patients in the placebo group (P = .004) required a high dose of benzodiazepines (20 mg or more of lorazepam) during the 72-hour period to control symptoms of AWS.

Baclofen Can Ease Symptoms of Acute Alcohol Withdrawal

Ингибиторы холинэстеразы при делирии

Use of the cholinesterase inhibitor rivastigmine (Exelon; Novartis) does not decrease the duration of delirium in critically ill patients in intensive care units (ICUs) when added to standard treatment with haloperidol, and might increase the risk for death, according to results of a large, placebo-controlled trial published online November 5 in The Lancet.

No Benefit, Possible Harm With Cholinesterase Inhibitor for Delirium

Эффективность приёма антипсихотика через день

Objective: In the treatment of schizophrenia, all currently available oral antipsychotics are administered at least once daily, with strict adherence strongly encouraged to minimize risk of relapse. Based on a better understanding of the brain kinetics of antipsychotics, we have proposed a variation of this approach, “extended” dosing, which allows for intermittent but regular dosing.

Method: We carried out a randomized, double-blind, placebo-controlled trial evaluating 35 individuals with DSM-IV–defined schizophrenia who had been stabilized on antipsychotic therapy. Over a 6-month interval, 18 subjects received their medication as usual (daily), while 17 received their antipsychotic therapy every second day (extended). Outcome measures included clinical scales to assess symptoms (Brief Psychiatric Rating Scale [the primary outcome measure], Calgary Depression Scale), illness severity (Clinical Global Impressions-Severity of Illness scale), and relapse (ie, rehospitalization) rates. Side effects were also assessed, including movement disorders (Barnes Akathisia Scale, Simpson-Angus Scale, Abnormal Involuntary Movement Scale) and weight. The study was conducted from February 2003 to July 2007.

Results: Individuals in the extended dosing group were not at greater risk of symptom exacerbation, relapse, or rehospitalization; indeed, more rehospitalizations occurred in those receiving regular dosing. At the same time, though, there was no indication that side effects were significantly reduced in the extended dosing group.

Conclusions: These results challenge the long-standing dogma that oral antipsychotics must be administered daily in stabilized patients with schizophrenia. Further studies with larger samples are needed to replicate these findings, as well as to elucidate whether postulated clinical advantages can be established and determined to outweigh potential risks.

“Extended” Antipsychotic Dosing in the Maintenance Treatment of Schizophrenia: A Double-Blind, Placebo-Controlled Trial

Окситоцин и негативная симптоматика шизофрении

Oxytocin is a hormone that has been reported to reduce the severity of schizophrenia when administered intra-nasally. Rubin and colleagues from the University of Illinois at Chicago report that women with schizophrenia showed less severe symptoms on the Positive and Negative Syndrome Scale (PANSS) in the mid-luteal phase compared with the follicular phase. Higher oxytocin levels in both men and women were associated with more prosocial behaviors. This lends credence to the potential usefulness of oxytocin in schizophrenia, which also is being studied in autism. As a researcher, I also think this study points to the possibility that PANSS ratings in clinical trials of antipsychotics should control for the menstrual phase to avoid the confounding effects of a decline in severity of psychosis during the mid-luteal phase irrespective of drug treatment.

Oxytocin is a hormone that has been reported to reduce the severity of schizophrenia when administered intra-nasally. Rubin and colleagues from the University of Illinois at Chicago report that women with schizophrenia showed less severe symptoms on the Positive and Negative Syndrome Scale (PANSS) in the mid-luteal phase compared with the follicular phase. Higher oxytocin levels in both men and women were associated with more prosocial behaviors. This lends credence to the potential usefulness of oxytocin in schizophrenia, which also is being studied in autism. As a researcher, I also think this study points to the possibility that PANSS ratings in clinical trials of antipsychotics should control for the menstrual phase to avoid the confounding effects of a decline in severity of psychosis during the mid-luteal phase irrespective of drug treatment.

Peripheral oxytocin is associated with reduced symptom severity in schizophrenia

Влияние гипертензии и индекса массы тела на когнитивные функции больных шизофренией

Objective: In recent years there has been a greater appreciation of the elevated prevalence of cardiovascular risk factors in the schizophrenia population and the liability some treatments have for their development. These vascular risk factors are in turn important risk factors in the development of dementia and more subtle cognitive impairments. However, their impact on the cognitive functions of patients with schizophrenia remains underexplored. The authors investigated whether vascular risk factors influence the cognitive impairments of schizophrenia and whether their effects on cognition in schizophrenia are different from those observed in nonpsychiatric comparison subjects.

Method: The authors compared 100 patients with schizophrenia and 53 comparison subjects on cognitive test performance in 2x2 matrices composed of individual vascular risk factors and group (schizophrenia patients and comparison subjects).

Results: Hypertension exerted a significant negative effect on immediate delayed and recognition memory in both groups. Patients with schizophrenia and hypertension were adversely affected in recognition memory, whereas comparison subjects were not. A body mass index above 25 was associated with negative effects on delayed memory in both groups, although the association fell short of statistical significance.

Conclusions: Given that patients with schizophrenia have a higher prevalence of vascular risk factors than the general population and are undertreated for them, treatment of these risk factors may significantly improve cognitive outcome in schizophrenia.

The Effects of Hypertension and Body Mass Index on Cognition in Schizophrenia

Виагра, когнитивные функции, негативная симптоматика шизофрении

We know that sildenafil (Viagra) helps restore erectile functioning, but not many people know that it also has cognitive-enhancing and neuroprotective effects in rodents. A double-blind, placebo-controlled study from Iran by Akhondzadeh et al suggests that sildenafil can significantly improve negative symptoms of schizophrenia. The study may lead to an important adjunctive use of this drug if it is replicated with a larger sample. The putative mechanism is the inhibition of phosphodiesterase 5 (PDE5), resulting in increased cyclic guanosine monophosphate (cGMP), which may correct the hypofunctioning N-methyl-D-aspartic acid (NMDA) glutamate receptor believed to be associated with elevated dopamine in the mesolimbic tract (causing positive symptoms) and a decline in dopamine in the mesocortical tract (causing cognitive deficits and negative symptoms).

Sildenafil adjunctive therapy to risperidone in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled trial

Свекла, нитраты и мозг

Drinking beet juice increases blood flow to the brain in older people, a finding that suggests the dark red vegetable may fight the progression of dementia, a new study shows.

Beet roots contain high concentrations of nitrates, which are converted into nitrites by bacteria in the mouth. And nitrites help open blood vessels in the body, increasing blood flow and oxygen to places lacking in oxygen.

Previous studies have shown that nitrites -- also found in high concentrations in celery, cabbage, and other leafy, green vegetables like spinach -- widen blood vessels, but researchers say this was the first to find that nitrites also increase blood flow to the brain.

Beet Juice Good for Brain

Терапия генерализованного тревожного расстройства

Studies comparing antidepressants with benzodiazepines in the treatment of GAD showed that although benzodiazepines work quickly, the antidepressants lower anxiety more effectively in the long term.[11] Antidepressants that have been approved by the United States Food and Drug Administration (FDA) for the treatment of GAD are extended-release venlafaxine,[12] duloxetine,[13] escitalopram,[14] and paroxetine.[15] Although not FDA approved, citalopram has also been found to be effective for the treatment of GAD.[16] Whereas benzodiazepines have been shown effective for shortterm anxiety, they may worsen depression, a common comorbidity of GAD, and cause other cognitive adverse effects such as sedation and anterograde amnesia. Individuals with a history of substance abuse or dependence should not use benzodiazepines, but patients with no such history rarely abuse these agents and can use them safely.[17] Buspirone and pregabalin also have proven efficacy for GAD.[18–21]

Table 1. Summary of Clinical Trials of Adjunctive Use of Atypical Antipsychotics for Treatment-Resistant Generalized Anxiety Disorder^a

Agent	Study Design	No. of Patients	Study Duration (wks)	Mean Daily Dose (mg)	Change in Assessment Score	Mean Weight Gain (lbs)b
Aripiprazole[30]	Open label	17	4.9	16.9	CGI-S: −1.6	NR
Aripiprazole[31]	Open label	10	9	NR	HAM-A: −20.6	7.1
Aripiprazole[32]	Open label	9	6	13.9	HAM-A: −12 CGI-I: 8 of 9 patients rated as much improved or very much improved	NR
Aripiprazole[33]	Open label	23	8	10.5	HAM-A: −6.7 CGI-S: −1	2.5
Olanzapine[34]	Randomized, controlled	21	6	8.7	HAM-A: olanzapine −7 vs placebo −3.9 (p=0.4) CGI-S: 67% of patients rated as not at all ill or borderline ill	11
Quetiapine[35]	Randomized, controlled	58	8	182	HAM-A: quetiapine −12.5 vs placebo −5.9 (p=0.002)	5.2
Quetiapine[36]	Randomized, controlled	22	8	120	HAM-A: quetiapine −2.6 vs placebo −0.3 (p=0.98)	2.7
Quetiapine[37]	Open label	40	12	386	HAM-A: −20.6	1.1
Risperidone[38]	Open label	16	8	1.12	HAM-A: −6.75 CGI-S: −1.53	3.9
Risperidone[39]	Randomized, controlled	40	5	1.1	HAM-A: risperidone −9.8 vs placebo −6.2 (p=0.034)	2.3
Risperidone[40]	Randomized, controlled	390	4	0.86	HAM-A: risperidone −9.26 vs placebo −9.12 (p=0.858) PaRTS-A: risperidone −8.54 vs placebo −7.61 (p=0.265)	2.65
Ziprasidone[41]	Open label	13	7	40	HAM-A: −11.2	0.2

HAM-A = Hamilton Rating Scale for Anxiety (lower scores indicate less severe symptoms of anxiety); CGI-S = Clinical Global Impressions-Severity (lower scores indicate less severe illness); CGI-I = Clinical Global Impression–Improvement; NR = not reported; PaRTS-A = Patient-Rated TroublingSymptoms for Anxiety.
^aAll atypical antipsychotic treatment was added to current antidepressant therapy.
^bIn patients who received the atypical antipsychotic.

Adjunctive Use of Atypical Antipsychotics for Treatment-resistant Generalized Anxiety Disorder

Атеросклероз и депрессия

Atherosclerosis does not appear to increase the risk for incident depression in older adults — a finding that runs contrary to the so-called vascular depression hypothesis, which asserts that vascular factors precede the onset of depression in this patient population.

No Link Between Atherosclerosis and Increased Depression Risk

Средство от эмоциональной лабильности при органических поражениях головного мозга

The US Food and Drug Administration (FDA) has approved dextromethorphan HBr and quinidine sulfate 20 mg/10 mg capsules (Nuedexta; Avanir Pharmaceuticals, Inc) as the first treatment for pseudobulbar affect (PBA).

PBA occurs secondary to brain injury or neurologic conditions such as multiple sclerosis, amyotrophic lateral sclerosis (ALS), and stroke. Also known as emotional incontinence, it is characterized by sudden outbursts of involuntary crying and/or laughing that can cause anxiety and embarrassment in public settings.

FDA Approves First Treatment for Pseudobulbar Affect

Шизофреноподобный психоз при болезни Альцгеймера с ранним началом

Our patient was a 65-year-old right-handed woman. In August 2003, her family noticed her mild memory disturbance, and she developed delusions that someone intruded into her house, always watched her, and stole her bankbook. In March 2005, she developed auditory hallucinations that someone told her bad things. She also insisted that someone let snakes loose in her house and that someone hid himself under the stool and watched her. She was first diagnosed with schizophrenia and prescribed risperidone. At the next visit, the Mini-Mental Status Examination was administered and she scored 21/30. MRI showed mild diffuse brain atrophy, and SPECT showed right-dominant decreased rCBF in the temporoparietal lobe. Considering these results, her diagnosis was changed to early-onset Alzheimer’s disease. Donepezil was prescribed, and her psychoses were improved.

Schizophrenia-Like Psychosis and Dysfunction of the Right-Dominant Temporoparietal Lobe in Early-Onset Alzheimer’s Disease

Кетамин и депрессия

Their article describes robust, clinically relevant, and rapid alleviation of depression symptoms in patients with bipolar disorder that persists far beyond the presence of the drug in the body. Ketamine has a terminal half-life of approximately 3 hours. Yet after 2 days, or 16 half-lives, of ketamine, the effect size of its antidepressant effects was large (0.8). Impressively, at 2 weeks there were still traces of the antidepressant effects of single ketamine dose, associated with an effect size of 0.22.

N- methyl-D-aspartate Glutamate Receptor Antagonists and the Promise of Rapid-Acting Antidepressants

Аффективные расстройства быстрого цикла ассоциированные с менструальным циклом

Affective fluctuations during menstruation have drawn considerable interest from researchers for a long time.1 Data indicates increased frequency of depression associated with menstrual period in adolescence,2 though there is limited information about the differences in the course or symptoms of bipolar disorder associated with menstrual period in adolescents. The question of the direction of mood shifts in the course of bipolar disorder with specific phases of menstrual cycle has been raised, albeit with limited and inconsistent results.3 We present a case of an adolescent female with cyclic affective changes akin to rapid cycling bipolar disorder starting in the premenstrual (luteal) period and subsiding with onset of menstruation, and we try to explore the biological underpinnings of inherent propensity for the development of bipolar disorder using quantitative electroencephalography (qEEG)

There was high spectral power in low frequency (theta band) over the right temporal region which was further corroborated by LORETA and revealed high signal density over the right temporal region for the same frequency band

A review3 presented findings of 24 prospective studies of affective fluctuations during the menstrual cycle. In most cases the authors found that negative moods marked by irritability, restlessness, anxiety, tension, migraine, sleep disturbance, and impaired concentration occurred more often during the premenstrual and menstrual phases than at other times in the cycle. There were only a few cases of positive moods—such as an increased feeling of well-being, elation, pleasantness, and activation—during the follicular and midcycle phases.3 This case presents with positive mood state, though irritability and headache were present as seen in premenstrual syndrome (PMS). This is an atypical presentation of PMS as opposed to the more common occurrence of elated moods during midcycle; in our case it occurred in premenstrual phase.7 It has been reported that whereas menstrual problems appear to occur more frequently in younger than in older women, premenstrual symptoms occur more often in older women. This suggests a relation between age and menstrual symptoms.

The overlap in symptomatology between PMS and cyclothymia, often considered to be a variant of manic-depressive illness, has given rise to therapeutic trials of lithium carbonate in women with PMS, with mixed results.14 Lithium treatment has been beneficial in controlling premenstrual affective changes, and this led us to use the same in our case.

Rapid Cycling Associated With Menstrual Periods in an Adolescent: Electrophysiological Underpinnings for Bipolarity

Натуральные источники серотонина, мелатонина и триптофана

There are some high-content sources of serotonin, melatonin, and tryptophan which can provide the body with these substances. These include plantains, pineapples, bananas, kiwis, plums, and tomatoes for serotonin; white and black mustard, wolfberry seeds, and fenugreek seeds for melatonin; and cottage cheese, soy protein, peanuts, beans, wheat flour, and potatoes for tryptophan

Depression and Fruit Treatment

Нейротоксичность лития при нормальных концентрациях

To the Editor: Lithium is used with great success in the treatment and prophylaxis of bipolar disorders, unipolar recurrent depression, and endogenous depression that is resistant to conventional treatment. It is also known to be neurotoxic at higher serum levels. In rare cases patients develop symptoms of intoxication even with normal lithium levels.

Case Report

A 61-year-old man with history of bipolar disorder that was managed with lithium for more than 20 years presented with complaints of psychomotor slowdown, unsteady gait, memory deficits, restlessness, sleep disorder, and severe tremor in his hand that prevented him from eating or drinking properly. These symptoms had begun in the previous week. There was no recent history of fever, respiratory, gastrointestinal, or urinary complaints. He was medicated with lithium, 800 mg/day, and fluvoxamine, 200 mg/day, and the dosage of his medication had remained unchanged over the last year.

Neurological examination showed psychomotor slowdown, inattention, temporal disorientation, severe episodic memory impairment, motor and verbal perseveration, slurred speech, and hypophonia. Symmetrical global and segmental bradykinesia and lead-pipe rigidity, as well as tremor at rest, intention, and posture, were also evident. His gait was abnormal with shuffling small steps and a hunched-forward upper body.

An analytic study revealed no abnormalities, including CBC, renal, thyroid and hepatic function, and PCR. Lithium serum levels were normal (1.0 mmol/liter).

EEG showed diffuse slow background activity, mainly at 5–6 Hz, with periods of greater lentification at 3 Hz, which is compatible with moderate to severe encephalopathy. A brain CT was normal. The patient was admitted and lithium was stopped. There was remarkable clinical improvement over the next days, and he was discharged at day 5, asymptomatic and on valproic acid (300 mg/day).

Lithium Neurotoxicity at Normal Serum Levels

Дисфагия при приёме палиперидона

Paliperidone-Induced Dystonic Dysphagia