Delfina Janiri

Neurodevelopment in Schizophrenia: The Role of the Wnt Pathways

Objectives. To review the role of Wnt pathways in the neurodevelopment of schizophrenia. Methods: Systematic PubMed search, using as keywords all the terms related to the Wnt pathways and crossing them with each of the following areas: normal neurodevelopment and physiology, neurodevelopmental theory of schizophrenia, schizophrenia, and antipsychotic drug action. Results: Neurodevelopmental, behavioural, genetic, and psychopharmacological data point to the possible involvement of Wnt systems, especially the canonical pathway, in the pathophysiology of schizophrenia and in the mechanism of antipsychotic drug action. The molecules most consistently found to be associated with abnormalities or in antipsychotic drug action are Akt1, glycogen synthase kinase3beta, and beta-catenin. However, the extent to which they contribute to the pathophysiology of schizophrenia or to antipsychotic action remains to be established. Conclusions: The study of the involvement of Wnt pathway abnormalities in schizophrenia may help in understanding this multifaceted clinical entity; the development of Wnt-related pharmacological targets must await the collection of more data.

Childhood traumatic experiences of patients with bipolar disorder type i and type II

BACKGROUND Childhood trauma is an important environmental stressor associated with bipolar disorders (BD). It is still not clear if it is differently distributed between BD I and BD II. Therefore, the aim of this research was to investigate the distribution patterns of childhood trauma in BD I and BD II. In this perspective, we also studied the relationship between childhood trauma and suicidality. METHODS We assessed 104 outpatients diagnosed with BD I (n=58) or BD II (n=46) according to DSM-IV-TR criteria and 103 healthy controls (HC) matched for age, sex and education level. History of childhood trauma was obtained using the Childhood Trauma Questionnaire (CTQ). RESULTS All patients with BD had had more severe traumatic childhood experiences than HC. Both BD I and BD II patients differed significantly from HC for trauma summary score and emotional abuse. BD I patients differed significantly from HC for sexual abuse, and BD II differed from HC for emotional neglect. BD I and BD II did not significantly differ for any type of trauma. Suicide attempts were linked to both emotional and sexual abuse in BD I and only to emotional abuse in BD II. Emotional abuse was an independent predictor of lifetime suicide attempts in BD patients. LIMITATIONS The reliability of the retrospective assessment of childhood trauma experiences with the CTQ during adulthood may be influenced by uncontrolled recall bias. CONCLUSIONS The assessment of childhood trauma, which has great clinical importance because of its strong link with suicidality, can unveil slight differences between BD subtypes and HC.

Executive functions in obsessive–compulsive disorder: An activation likelihood estimate meta-analysis of fMRI studies

Abstract Objectives: To identify activation changes assessed in functional magnetic resonance imaging (fMRI) studies of obsessive–compulsive disorder (OCD) through Activation Likelihood Estimate meta-analysis. Methods: We included 28 peer-reviewed standard stereotactic space studies assessing adult OCD patients (OCDpts) vs. healthy controls (HCs) with fMRI during executive task performance. Results: In within-group analyses, HCs showed task-related activations in bilateral inferior frontal gyri, right middle frontal gyrus, right inferior parietal lobule, right claustrum, bilateral cingulate gyri, and left caudate body. OCDpts showed task-related left-sided activations in the superior, medial, and inferior frontal gyri, and thalamus, and bilateral activations in the middle frontal gyri, inferior parietal lobule, and insular cortices. Subtraction analysis showed increased left middle frontal gyrus activation in OCDpts. In between-groups analyses, OCDpts hypoactivated the right caudate body, left putamen, left ACC, and right medial and middle frontal gyri. Right caudate hypoactivation persisted also after applying Family‐wise error algorithms. Conclusions: This meta-analysis confirms that during executive functioning OCDpts show a functional deficit of the right caudate body, which could represent a major neural functional correlate of their illness.

Gray and white matter trajectories in patients with bipolar disorder

Findings on brain structural abnormalities in patients with bipolar disorder (BP) are inconsistent and little is known about age‐related evolution of these changes. We employed a cross‐sectional, case–control study to compare structural age‐related brain trajectories in patients with BP and healthy control subjects (HC) over a period of approximately 50 years. The primary aim was to understand whether white (WM) and gray matter (GM) abnormalities are present from the beginning of the illness and how they change over time.

Intramuscular Aripiprazole in the Acute Management of Psychomotor Agitation

To assess acute efficacy and safety of 9.75 mg of intramuscular (IM) injections of the atypical antipsychiatric aripiprazole in patients with schizophrenia or bipolar disorder and acute agitation.

Are 5-HT3 antagonists effective in obsessive-compulsive disorder? A systematic review of literature

The purpose of this literature database search‐based review was to critically consider and evaluate the findings of literature focusing on efficacy and safety of 5‐HT3 antagonists in the treatment of obsessive–compulsive disorder (OCD), so as to test whether preclinical data match clinical therapeutic trials.

Amygdala and hippocampus volumes are differently affected by childhood trauma in patients with bipolar disorders and healthy controls

Volumetric studies on deep gray matter structures in bipolar disorder (BP) have reported contrasting results. Childhood trauma, a relevant environmental stressor for BP, could account for the variability of the results, modulating differences in the amygdala and hippocampus in patients with BP compared with healthy controls (HC). Our study aimed to test this hypothesis.

Mitochondrial myopathy and comorbid major depressive disorder: effectiveness of dTMS on gait and mood symptoms

BACKGROUND Mitochondrial myopathies (MMs) often present with leukoencephalopathy and psychiatric symptoms, which do not respond to or worsen with psychiatric drugs. CASE REPORT A 67-year-old woman with a 10-year history of probable chronic progressive external ophthalmoplegia, an MM, had drug-resistant, anxious-depressive symptoms. Since she had never had seizures, we proposed 20 sessions of deep transcranial magnetic stimulation (dTMS) for her depression. Surprisingly, besides the expected improvement of depression, we observed marked improvement of movement disorder that lasted as long as the patient was undergoing dTMS. She also improved her performance on neuropsychological tests of executive function and cognitive speed. Depressive symptom improvement was persistent, while anxiety symptoms recurred after the end of the sessions. CONCLUSIONS dTMS may be an alternative antidepressant strategy in patients with MMs, provided that they are free from seizures. The mechanism of improvement of motor disturbance may relate to dorsolateral prefrontal cortex stimulation and improved executive function and needs further investigation.

Neural functional correlates of empathic face processing

OBJECTIVES Empathy is a human trait related to the ability to share someone elses feelings, and emotional face processing is one of its measures. Functional Magnetic Resonance Imaging (fMRI) studies showed significant neural correlates of empathic face processing. We aimed to identify those brain areas most consistently involved in empathy for emotional faces. METHODS We carried ALE meta-analysis of whole-brain data from fMRI studies during empathic face-processing tasks. We included 23 studies conducted on a total of 568 participants (247 males and 321 females, mean age 32.2 years). RESULTS Emotional vs. control faces processing significantly correlated with activations of the left anterior cingulate cortex (BA 32), right precentral gyrus (BA 6), left amygdala, right superior frontal gyrus (BA 9), left middle occipital gyrus (BA 37), right insula (BA 13), left putamen, and left posterior cingulate cortex (BA 31). CONCLUSIONS Empathy is a complex process correlating with bi-hemispheric cortico-limbic activations involved in emotional cue processing, self-other/same-different discrimination, perspective-taking, theory of mind, emotional arousal, and decision-making.

Neurobiological Evidence for the Primacy of Mania Hypothesis

Background: Athanasios Koukopoulos proposed the primacy of mania hypothesis (PoM) in a 2006 book chapter and later, in two peer-reviewed papers with Nassir Ghaemi and other collaborators. This hypothesis supports that in bipolar disorder, mania leads to depression, while depression does not lead to mania. Objective: To identify evidence in literature that supports or falsifies this hypothesis. Method: We searched the medical literature (PubMed, Embase, PsycINFO, and the Cochrane Library) for peer-reviewed papers on the primacy of mania, the default mode function of the brain in normal people and in bipolar disorder patients, and on illusion superiority until 6 June, 2016. Papers resulting from searches were considered for appropriateness to our objective. We adopted the PRISMA method for our review. The search for consistency with PoM was filtered through the neurobiological results of superiority illusion studies. Results: Out of a grand total of 139 records, 59 were included in our analysis. Of these, 36 were of uncertain value as to the primacy of mania hypothesis, 22 favoured it, and 1 was contrary, but the latter pooled patients in their manic and depressive phases, so to invalidate possible conclusions about its consistency with regard to PoM. All considered studies were not focused on PoM or superiority illusion, hence most of their results were, as expected, unrelated to the circuitry involved in superiority illusion. A considerable amount of evidence is consistent with the hypothesis, although indirectly so. Limitations. Only few studies compared manic with depressive phases, with the majority including patients in euthymia. Conclusion: It is possible that humans have a natural tendency for elation/optimism and positive self-consideration, that are more akin to mania; the depressive state could be a consequence of frustrated or unsustainable mania. This would be consistent with PoM.