Methylphenidate (MPD) is a drug prescribed for the treatment of attention deficit/hyperactivity disorder and its therapeutic effect is attributed to the inhibition of dopamine.

Young male Wistar rats were administered MPD (1, 2, 5, or 10 mg/kg) once a day or an intraperitoneal injection of saline for 28 days (chronic treatment) or for 1 day (acute treatment). Two hours after the last administration the animals were decapitated and their striatum was dissected.

In this work, we show that continued treatment with MPD is capable of modifying the levels of phosphorylation of proteins JNK1/2 (c-Jun amino-terminal kinases 1 and 2) and ERK1/2 (extracellular signal-regulated kinases 1 and 2). Whereas the level of phosphorylation of protein ERK increased significantly, that of proteins JNK1/2 diminished.

The alteration in the level of activation of mitogen-activated protein kinases can be a molecular mechanism through which MPD exerts its therapeutic effect.

Recent genetic studies have revealed that the interleukin (IL) 1 gene complex is associated with schizophrenia in the Caucasian population; however, data from the North African population are limited. To further assess the role of interleukin 1 receptor antagonist protein (IL1Ra) in schizophrenia, we examined a functional multiallelic polymorphism localised in intron 2 of this receptor gene associated with an altered level of IL1Ra.

In the present case–control study, we have analysed the (86 bp)n polymorphism of the interleukin 1 receptor antagonist (IL1RN) gene (RS 1794068) by polymerase chain reaction genotyping in 259 patients with schizophrenia and 178 healthy controls from the Tunisian population.

We showed that the frequencies of the IL1RN*2/2 genotype and allele 2 were higher in the patient group compared with the control group, and the difference was statistically significant [13.5% vs. 5.6%, p = 10−3, odds ratio (OR) = 3.2% and 32.8% vs. 21.9%, p = 3 × 10−4, OR = 1.76, respectively). When we evaluated the association between this genetic polymorphism and the clinical variables of schizophrenia, we found that the frequencies of the 2/2 genotype and allele 2 were significantly higher in the male patient group (p = 10−4 and 10−5, respectively) compared with the male control group, indicating a substantially increased risk for sex-onset schizophrenia with inheritance of the IL1RN2 allele. When the association between the genotypes and outcome was evaluated by multiple logistic regression analysis, the adjusted OR for the IL1RN genotypes remained statistically significant [1.39; 95% confidence interval (CI) = 1.11–1.73; p = 0.003].

The intron 2 polymorphism in IL1RN or a genetic polymorphism at proximity seems to be associated specifically with schizophrenia in the Tunisian male population.

Motor retardation is a characteristic feature of bipolar depression, and is also a core feature of Parkinson's disease. Within the framework of the functional deafferentiation theory in Parkinson's disease, we hypothesised that motor retardation in bipolar depression is mediated by disrupted subcortical activation, leading to decreased activation of cortical motor areas during finger tapping.

We used functional magnetic resonance imaging to investigate neural activity during self-paced finger tapping to elucidate whether brain regions that mediate preparation, control and execution of movement are activated differently in subjects with bipolar depression (n = 9) compared to healthy controls (n = 12).

An uncorrected whole-brain analysis revealed significant group differences in dorsolateral and ventromedial prefrontal cortex. Corrected analyses showed non-significant differences in patients compared to controls: decreased and less widespread activation of the left putamen and left pallidum; increased activity in the left thalamus and supplementary motor area; decreased activation in the left lateral pre- and primary motor cortices; absence of activation in the pre-supplementary motor area; activation of the bilateral rostral cingulate motor area.

Both movement preparation and execution may be affected in motor retardation, and the activity in the whole left-side motor circuit is altered during self-initiated motor performance in bipolar depression.

To verify the prevalence and clinical impact of excessive daytime sleepiness (EDS) in outpatients with bipolar disorder.

Eighty‐one outpatients with bipolar disorder and 79 healthy control subjects were recruited. Patients were required not to be acutely manic or depressed. We used the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index and the Functioning Assessment Short Test to assess sleepiness, sleep problems and functioning, respectively.

Patients had a higher prevalence of sleepiness (40%) than the control group (18%). Sleepiness and sleep disturbance had independent impacts on disability in the multivariable model.

This study suggests that EDS is a relevant clinical dimension in patients with bipolar disorder. It is a frequent symptom that often overlaps with other sleep disturbances. This study also reveals that once present it has the potential to increase functional impairment.

ConstaTRE is an open-label, randomised, controlled, relapse prevention trial in patients with stable schizophrenia or schizoaffective disorder switched to risperidone long-acting injectable (RLAI) or oral quetiapine, and was designed to test the hypothesis that injectable antipsychotic treatment with risperidone would be more effective than oral therapy with quetiapine. Here we report the functional recovery results from the ConstaTRE trial.

Clinically stable adults previously treated with oral risperidone, olanzapine, or oral first-generation antipsychotics were randomised to RLAI or quetiapine for 24 months. Functional recovery was assessed using the Social and Occupational Functioning Assessment Scale (SOFAS) and two quality-of-life (QoL) measures [Medical Outcomes Survey Short Form-12 (SF-12) and Schizophrenia Quality-of-Life Scale Revision 4 (SQLS-R4)].

A total of 666 patients were randomised and treated with RLAI (n = 329) or quetiapine (n = 337). Relapse occurred in 16.5% RLAI and 31.3% quetiapine patients. Significant improvements in SOFAS, SF-12, and SQLS-R4 scores were observed from baseline to month 24 with both RLAI and quetiapine. At months 6, and 12, and endpoint, improvement in SOFAS score was significantly greater for RLAI than quetiapine (p < 0.05).

Among patients with stable schizophrenia or schizoaffective disorder, the likelihood of functional recovery appears to be higher in those switching to RLAI than to quetiapine, although improvements in functional status and QoL were observed with both treatments.

The primary aim of this explorative study was to investigate the influence of the glutamatergic N‐methyl‐d‐aspartate (NMDA) receptor antagonist memantine on motor activity in healthy subjects. Secondarily, we wanted to compare these data to findings in a sample of schizophrenia patients.

The healthy subjects acted as their own controls in an open‐within‐subject design. Motor activity was recorded with an actigraph worn for 24 h in the drug‐free, and steady‐state memantine conditions, respectively. Motor activity levels for 1‐min intervals were analysed by means of both linear and nonlinear methods. The schizophrenia patients were monitored only once, without memantine manipulation.

The root mean square successive differences (RMSSD) and the RMSSD/SD ratio were increased by memantine, and memantine was also associated with lower autocorrelation (lag 1) but in recordings from the right arm only. These movement patterns partly corresponded to those found in a sample of drug‐treated schizophrenia patients. Total activity level, standard deviation (SD) and sample entropy were not significantly different in the memantine versus drug‐free condition.

The findings suggest a role for the NMDA receptor in the regulation of motor activity in healthy individuals as memantine increased the variability in the motor recordings and the alterations between adjacent motor recordings. It is suggested that the findings may be relevant to the role played by glutamate and the NMDA receptor functioning to the motor disturbances in schizophrenia.

To investigate the relationships between single-nucleotide polymorphisms (SNPs) in NOTCH4 and brain-derived neurotrophic factor (BDNF) with schizophrenia among Han Chinese in Southern China.

Two NOTCH4 SNPs (rs520688 and rs415929) and two BDNF SNPs (rs2030324 and rs12273539) were examined in 464 schizophrenics and 464 healthy controls from Hunan province in South China, using the Sequenom MassARRAY® iPLEX System.

In the study population, rs520688 and rs2030324 were significantly associated with schizophrenia. A decreased risk of schizophrenia was associated with the rs520688 GA genotype (p = 0.035), whereas an increased risk of schizophrenia was associated with the rs2030324 CC/CT genotype (p = 0.044). The genotype distributions of rs415929 in NOTCH4 and rs12273539 in BDNF did not differ significantly between the case and control groups. Although no allele–allele interactions were detected between rs520688 and rs2030324, recombination analysis revealed a combined effect of the two on the susceptibility to schizophrenia, with GA-TT decreasing and CT/CC-GG/GA increasing the risk of schizophrenia.

In conclusion, rs520688 in NOTCH4 and rs2030324 in BDNF are significantly associated with schizophrenia among Han Chinese in Southern China. The two had a combined effect on the susceptibility to schizophrenia among Han Chinese in Southern China, but this may not be caused by an allele–allele interaction.

Delirium syndrome is common in the hospitalised population. However, data on its aetiological factors are scarce. Clinical observations suggest a relationship between delirium occurrence and seasons. The aim of study was to determine whether a seasonal variation exists in the occurrence of delirium events in‐hospital patients.

The study included all admissions to the medical units of the Hospital of Ferrara, Italy, between January 2002 and December 2010. On the basis of date admission, cases have been analysed for seasonal variation (four 3‐month intervals by seasons) by means of conventional statistics. Moreover, cases categorised into twelve 1‐month intervals were also analysed by means of a validated chronobiologic inferential method (single cosinor) to search for cyclic variability.

During the analysed period, the hospital database contained 74 379 records referring to 42 625 subjects (52.7% females). Delirium diagnoses were 1300 (1.7% of total sample), 668 of whom in females (51.4%) and 632 in males (48.6%). Events of delirium were more frequent in winter and autumn (26.6 and 26.5%, respectively) than in spring (23.5%) and summer (23.4%). Chronobiological analysis yielded a significant peak of delirium events in January, when considering both the total raw number of cases and the percent of admissions.

The study seems to indicate in patients hospitalised in medical units, a higher rate of occurrence of delirium in autumn‐winter, similar to that reported for acute medical diseases. The role of possible underlying favouring or triggering factors deserves further research.

To evaluate the efficacy of an early multidisciplinary (neurology and psychiatry) intervention for conversion disorder (CD).

Consecutive patients newly diagnosed with CD from 2005 to 2007 were compared to a control group of newly diagnosed CD patients receiving usual care. At 3 years, a questionnaire evaluated self‐rated subjective outcome, symptom severity, SF‐36 scores, employment status and medical care use.

Data from 12 cases (mean age 25.5 ± 8.2; 9 females) and 11 controls (mean age 34.7 ± 13.5; 10 females) showed that 83% of cases had a good subjective outcome (symptom improved or cured) when only 36% of controls had a good outcome (p < 0.05). Cases significantly improved their SF‐36 scores on subscales involving physical complaints compared to controls. A minority (20%) of cases reduced or ceased professional activity when 70% of controls did (p < 0.001). Only 16% of cases sought further medical advice for the initial symptom when 73% of controls did. Both groups accepted psychiatric referrals (83% of cases and 73% of controls) and found it beneficial.

Early intervention involving both neurologists and psychiatrists is effective for CD in alleviating physical complaints, reducing sick leave and health care use.

Intracranial epidermoid cysts are congenital cysts. They comprise 0.2–1.8% of primary intracranial tumours and are four to nine times as common as dermoid cysts.

We here in present the case of a 32-year-old man who reported sudden onset of symptoms of a depressive symptomatology and particularly severe headache, accompanied by fatigue, depressed mood most of the day, marked diminished interest or pleasure in all or almost all activities, insomnia and diminished ability to think or concentrate. Brain magnetic resolution imaging examination revealed a pineal epidermoid cystic lesion, visualised in the posterior part of the third ventricle, with a maximum diameter of ∼2.8 cm and obstructing the aqueduct of Sylvius, causing obstructive hydrocephalus.

Pineal cysts may enlarge over time, because of either increased cyst fluid or intracystic haemorrhage, and become symptomatic. Brain radiological investigations in patients with depressive symptomatology may be substantial.

To examine and record the clinical antidepressant effect of exogenous agmatine, an amino acid derived central glutamaergic modulator in endogenously depressed subjects. It was also the author's intention to examine the effects of parachlorophenylalanine (PCPA) in therapeutic responders to determine if serotonergic mechanisms mediate agmatine's antidepressant effect.

Exogenous agmatine was ingested in doses of 2‐3mg/day by depressed subjects with Major Depresssive Disorder (MDD), clinically assessed using the 21 item Hamilton Rating Scale for Depression (HAM‐D), the Clinical Global Impression (CGI) and the Brief Psychiatric Rating Scale (BPRS). Antidepressant responders volunteered to concommittantly ingest parachlorophenylalanine (PCPA) at starting doses of 250mg/day, and increased until depressive relapse, mitigating side effects, or a maximum dosage of 1250mg/day.

Three depressed subjects showing total illness remission with exogenous agmatine did not relapse after concomitantly adding PCPA. Effective in relieving both psychomotor agitation and retardation, the antidepressant effect was free of physical or behavioural side effects: gastrointestinal discomfort and loose stools in one subject resolved spontaneously within days. All three subjects refused to risk depressive relapse by temporarily stopping agmatine after PCPA was stopped.

The antidepressant effect of exogenous agmatine was documented in a small number of MDD subjects, and was not reversed/modified by PCPA confirming findings in animals that therapeutic response is not mediated by serotonergic mechanisms. A NAMDA (N‐methyl‐D‐aspartate) receptor antagonist, agmatine's recognized function in brain as inhibitory modulator of excitatory glutamatergic transmission suggests a pivotal role for brain glutamate, contributing to the ripening glutamatergic basis of depression, and a rational basis for future antidepressant pharmacotherapy.

Propranolol, the first discovered b-adrenergic receptor antagonist, has been prescribed by physicians in various fields for more than three decades. It has been applied for treating psychiatric disorders including schizophrenia, mania and anxiety disorders, as well as for controlling withdrawal symptoms or other side effects.

We describe the case of an 11-year-old boy with bipolar-I disorder comorbid with panic disorder who developed manic symptoms with a single dose of 10 mg of propranolol.

Although depression is a better-known side effect of b-adrenergic antagonists, clinicians should take mania as a rare side effect into consideration as well.

Marfan syndrome (MFS) is an autosomal dominant disorder of fibrillin-1 gene mutations, with the involvement of cardiovascular, skeletal, and ocular systems. In addition to physical abnormalities, MFS patients are also found to be susceptible to schizophrenia and other psychiatric conditions.

Awareness of the association between MFS and psychiatric conditions would improve the clinical management of MFS patients to reduce the risk or even to prevent the development of psychiatric complications in MFS patients.

Here, we describe a male MFS patient who manifested incoherent speech and impaired cognitive and social function at the age of 40 years.

His mental dysfunction could be attributed to his bilateral cerebral infarction, which is a neurovascular complication associated with MFS.

Behavioural symptoms are common in moderate to severe Alzheimer's disease (AD) and are improved by memantine with the most pronounced effect on agitation/aggression. Dextromethorphan in combination with quinidine is the only drug approved by US Food and Drug Administration for the treatment of pseudobulbar affect (PBA) on the basis of efficacy in patients with multiple sclerosis or amyotrophic lateral sclerosis. The aim of our study was to evaluate the efficacy of memantine on PBA in patients with AD.

In a prospective, double-blind, case-control study to assess PBA with pathological laughter and crying scale patients were administered memantine (final dose of 20 mg daily) or citalopram (20 mg once daily), each for 10 weeks. The number of episodes of involuntary emotional expression, Neuropsychiatric Inventory (NPI) and Overt Aggression Scale-Modified (OAS-M) total scores were also recorded. Furthermore, the platelet serotonin (5-HT) concentration was measured.

Although memantine had beneficial effects on PBA, it also had a crucial impact on behavioural symptoms, especially aggression and agitation (to an average of 3.5 times higher end-point scores on OAS-M and increase of NPI total scores for an average of 114% of initial value). Therefore, the study was prematurely stopped. In addition, we had evidenced a drop of platelet 5-HT concentration (to an average of 73% of initial value).

Surprisingly, our research showed the opposite action of memantine on neuropsychiatric symptoms as expected. In a limited number of AD patients with PBA, memantine had a beneficial effect on involuntary emotional expression, but it potentiated agitation/aggression, irritability and caused a crucial drop of the platelet 5-HT concentration.

To report a case of Pisa syndrome in a patient with idiopathic normal pressure hydrocephalus, who had never been exposed to psychotropic medications.

A 26-year-old, Colombian, male patient, was referred because he had cognitive abnormalities, gait disturbances and urinary incontinence. This patient also displayed pleurothotonos. Neurofunctional evaluations of sensory and motor integration at peripheral and central nervous system levels were done. Idiopathic normal pressure hydrocephalus (NPH) was diagnosed.

Pisa syndrome disappeared after spinal tap drainage with further gait, balance and behavioural improvement. A brainstem-thalamocortical deregulation of the central sensory and motor programming, due to the chaotic enlargement of brain ventricles was thought to be the pathophysiological mechanism underlying this case.

NPH must not be longer considered as an exclusive geriatric disorder. Further, uncommon movement disorders may appear with this disorder, which should be carefully approached to avoid iatrogenic and deleterious pharmacological interventions.

Trichotillomania (TTM) is a psychiatric syndrome characterised by the inability to control repetitive hair pulling. Psychiatric data reveal that TTM is not usually prevalent among all family members of patients, and so far only one case of familial TTM has been reported.

In this study, we report a case of familial TTM that afflicted four sisters and discuss the importance of genetic factors in this disorder.

This report suggests that, similar to many other psychiatric disorders, TTM can be detected in other family members and that genetic factors not only have a significant role in the development of such disorders but also in determination of the disorder subtype. This report also shows that the comorbidities in one member of the family might predict the existence of comorbidities in other members. On the basis of response to medication.

the authors suggest that a genetic disorder like polymorphism in serotonin receptors or dopamine can cause such a disorder.

Urgency, urinary incontinence and bowel disturbances are distressing side effects that have been observed during treatment with risperidone and other antipsychotics probably due to the receptor affinity profile. This occurrence can lead to poor compliance and therefore impair clinical outcome.

We report the case of a 50 year‐old lady, who experienced urinary incontinence and diarrhoea, when switching from oral to injectable risperidone, which ceased when discontinuing the drug.

It should be taken into account that some side effects can be revealed when switching from oral to depot formulations due to non‐compliance to orals; nevertheless dose‐dependent mechanisms and individual metabolic variability must be considered when observing idiosyncratic reactions to drugs.