BackgroundBipolar disorder is a chronic mood disorder with episodic progress and high relapse rate. Growing evidence suggests that individuals with bipolar disorder display cognitive impairment which persists even throughout periods of symptom's remission.Method137 bipolar patients met the inclusion criteria (depressive episode: DSM-IV-TR criteria for major depressive episode, HAMD score ≥17; manic/hypomanic episode: DSM-IV-TR criteria for manic/hypomanic episode, YMRS score ≥12, euthymic: 6 months of remission, HAMD score ≤8, YMRS score ≤6; and mixed: DSM-IV-TR criteria for mixed episode, HAMD score >8 and YMRS score >6) and were therefore enrolled in the study. Patients were free of psychotic symptoms (hallucinations/delusions) at the moment of testing. Control group consisted of 62 healthy subjects without history of neurological and/or psychiatric disorder. Cognitive battery has been applied in order to assess verbal memory, working memory, psychomotor speed, verbal fluency, attention and speed of information processing, and executive function. Following data were collected: demographics, psychiatric history, age of illness onset; current and previous treatment (including hospitalizations). Cognitive deficits were assessed in bipolar patients experiencing manic, depressive, mixed episodes or who were euthymic in mood. Results were compared between the subgroups and with healthy individuals. The association of impaired cognition with illness course was analyzed.ResultsBipolar patients showed cognitive deficits in all evaluated domains when compared to controls. The lowest scores were obtained for the verbal fluency test. After adjusting for current episode, manic subgroup showed greater cognitive impairment in verbal and working memory, executive function/reasoning and problem solving, compared to depressive, mixed, and euthymic subgroup. Low-neurocognitive performance was directly associated with a predominance of manic episodes and severe course of bipolar illness. An increased number of past manic episodes was the strongest correlated event with the poorest outcomes in verbal memory testing. Other factors correlated with poor verbal memory scores in manic subgroup were age at illness onset (positive correlation), illness length, and hospitalizations (negative correlations).ConclusionsBipolar patients showed cognitive deficits regardless of the phase of illness. Subjects experiencing a manic episode displayed higher deficits in verbal and working memory, executive function/reasoning, and problem solving. Severe course of illness also showed significant contribution in terms of cognitive impairment.

ClinicalTrials.gov identifier: NCT01280305.

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by social deficits and stereotyped behaviors. Despite intensive research, its etiopathogenesis remains largely unclear. Although studies consistently reported dopaminergic anomalies, a coherent dopaminergic model of ASD was lacking until recently. In 2017, we provided a theoretical framework for a “dopamine hypothesis of ASD” which proposed that autistic behavior arises from a dysfunctional midbrain dopaminergic system. Namely, we hypothesized that malfunction of 2 critical circuits originating in the midbrain, that is, the mesocorticolimbic and nigrostriatal pathways, generates the core behavioral features of ASD. Moreover, we provided key predictions of our model along with testing means. Since then, a notable number of studies referenced our work and numerous others provided support for our model. To account for these developments, we review all these recent data and discuss their implications. Furthermore, in the light of these new insights, we further refine and reconceptualize our model, debating on the possibility that various etiologies of ASD converge upon a dysfunctional midbrain dopaminergic system. In addition, we discuss future prospects, providing new means of testing our hypothesis, as well as its limitations. Along these lines, we aimed to provide a model which, if confirmed, could provide a better understanding of the etiopathogenesis of ASD along with new therapeutic strategies.

Background: There are only a few studies involving the use of melatonin for premedication for anaesthesia. The goal of our study was to compare the effects of melatonin and midazolam administered as premedication for laparoscopic cholecystectomy.Methods: This double-blind, placebo-controlled study included 53 patients (ASA I, II) undergoing laparoscopic cholecystectomy under general anaesthesia. The patients were divided into three groups: group 1 (n = 18) included patients receiving 3 mg melatonin the night before and as premedication; group 2 (n = 17) included the patients receiving 3,75 mg midazolam (1/2 of a 7,5 mg tablet) by the same protocol as for melatonin; and group 3 (n = 18) included patients receiving placebo tablets. Preoperatively, the anxiety and sedation scores, as well as the quality of preanaesthetic sleep, were evaluated. Postoperatively, the anxiety and sedation scores and the number of remembered pictures were evaluated at 15 and 60 minutes and 6, 12 and 24 hours respectively. The intra-anaesthetic opioid requirements were also evaluated.Results: Preoperatively the lowest anxiety score was registered in the midazolam group; also the difference between the melatonin and midazolam groups was not significant. In the placebo group the anxiety score was significantly higher as compared with melatonin or midazolam. Postoperatively anxiety scores were lowest in the melatonin group at every time interval. The scores for the remembered pictures were consistently better in the melatonin group. The sedation score was lower in the melatonin group as compared with midazolam, as were the intra-anaesthetic opioid requirements.Conclusions: Melatonin (3 mg) can be successfully used as premedication for laparoscopic cholecystectomy, especially for day case surgery. Advantages over midazolam and placebo include better perioperative anxiolysis, and a better recovery profile as assessed by sedation and memory.

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BackgroundCognitive functions have been investigated across depressed, manic, hypomanic, mixed and euthymic episodes of bipolar disorder, but the stability or the progression of cognitive impairment is still under research.ObjectiveThe purpose of the present study was to assess the outcome of cognitive functions in bipolar patients following a depressive episode, after a 6-month period in the absence of mood symptoms.Method63 bipolar patients were tested with a battery of neurocognitive tests both at baseline (during an acute depressive episode) and after 6 months of euthymia. The cognitive domains assessed included memory, attention, verbal fluency, processing speed and executive functions. Cognitive performances were compared with those of a control group (40 healthy control subjects), both in depression and in euthymia.ResultsPatients scored worse than control subjects in several cognitive domains, both in depression and euthymia. The most impaired cognitive functions were executive functions and verbal memory. Between the two moments of assessment bipolar patients obtained a significant improvement in memory, verbal fluency, attention and information processing speed. Psychomotor speed showed no difference between depression and euthymia.ConclusionsBipolar patients showed impairment in several cognitive domains during depression. A certain degree of impairment remained even after the remission of the affective episode in relationship with the executive functions. Between depression and euthymia, bipolar patients showed important cognitive improvements.

The negative symptoms of schizophrenia are an unmet treatment target as currently approved treatments mostly control positive symptoms. The persistence of these symptoms holds back the patient's reinstatement in society, making them incapable of fulfilling their social, professional, or family roles. There is overwhelming research evidence suggesting that the negative symptoms of schizophrenia are associated with poorer functioning and lower quality of life than positive symptoms, confirming the need for developing new treatments for this particular category of symptoms. This present review aims to review clinical trials addressing novel pharmacological approaches addressing primary negative symptoms of schizophrenia. We overview both monotherapies, first-generation and second-generation antipsychotics, and add-on therapies, including psychostimulants, anti-inflammatory drugs, antidepressants, molecules targeting glutamatergic, cholinergic or serotonergic systems and hormones. Our findings suggest that the primary negative symptoms of schizophrenia may be mitigated by adjunctive therapies, and we highlight the pharmacological agents that have proven superior efficacy. Novel compounds such as cariprazine and MIN-101, to date, show promising results, but large clinical trials are needed to test their efficacy and safety.

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