Giuseppe Delvecchio

Common and distinct neural correlates of emotional processing in Bipolar Disorder and Major Depressive Disorder: A voxel-based meta-analysis of functional magnetic resonance imaging studies

Neuroimaging studies have consistently shown functional brain abnormalities in patients with Bipolar Disorder (BD) and Major Depressive Disorder (MDD). However, the extent to which these two disorders are associated with similar or distinct neural changes remains unclear. We conducted a systematic review of functional magnetic resonance imaging studies comparing BD and MDD patients to healthy participants using facial affect processing paradigms. Relevant spatial coordinates from twenty original studies were subjected to quantitative Activation Likelihood Estimation meta-analyses based on 168 BD and 189 MDD patients and 344 healthy controls. We identified common and distinct patterns of neural engagement for BD and MDD within the facial affect processing network. Both disorders were associated with increased engagement of limbic regions. Diagnosis-specific differences were observed in cortical, thalamic and striatal regions. Decreased ventrolateral prefrontal cortical engagement was associated with BD while relative hypoactivation of the sensorimotor cortices was seen in MDD. Increased responsiveness in the thalamus and basal ganglia were associated with BD. These findings were modulated by stimulus valence. These data suggest that whereas limbic overactivation is reported consistently in patients with mood disorders, future research should consider the relevance of a wider network of regions in formulating conceptual models of BD and MDD.

Subcortical volumetric abnormalities in bipolar disorder.

Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case–control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen’s d=−0.232; P=3.50 × 10−7) and thalamus (d=−0.148; P=4.27 × 10−3) and enlarged lateral ventricles (d=−0.260; P=3.93 × 10−5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.

Evidence of diagnostic specificity in the neural correlates of facial affect processing in bipolar disorder and schizophrenia: a meta-analysis of functional imaging studies.

BACKGROUND Schizophrenia (SZ) and bipolar disorder (BD) may overlap in etiology and phenomenology but differ with regard to emotional processing. We used facial affect as a probe for emotional processing to determine whether there are diagnosis-related differences between SZ and BD in the function of the underlying neural circuitry. METHOD Functional magnetic resonance imaging (fMRI) studies published up to 30 April 2012 investigating facial affect processing in patients with SZ or BD were identified through computerized and manual literature searches. Activation foci from 29 studies encompassing 483 healthy individuals, 268 patients with SZ and 267 patients with BD were subjected to voxel-based quantitative meta-analysis using activation likelihood estimation (ALE). RESULTS Compared to healthy individuals, when emotional facial stimuli were contrasted to neutral stimuli, patients with BD showed overactivation within the parahippocampus/amygdala and thalamus and reduced engagement within the ventrolateral prefrontal cortex (PFC) whereas patients with SZ showed underactivation throughout the entire facial affect processing network and increased activation in visual processing regions within the cuneus. Patients with BD showed greater thalamic engagement compared to patients with SZ; in the reverse comparison, patients with SZ showed greater engagement in posterior associative visual cortices. CONCLUSIONS During facial affect processing, patients with BD show overactivation in subcortical regions and underactivation in prefrontal regions of the facial affect processing network, consistent with the notion of reduced emotional regulation. By contrast, overactivation within visual processing regions coupled with reduced engagement of facial affect processing regions points to abnormal visual integration as the core underlying deficit in SZ.

DTI and Myelin Plasticity in Bipolar Disorder: Integrating Neuroimaging and Neuropathological Findings

Bipolar disorder (BD) is a major psychiatric illness with a chronic recurrent course, ranked among the worldwide leading disabling diseases. Its pathophysiology is still not completely understood and findings are still inconclusive, though a great interest on the topic has been constantly raised by magnetic resonance imaging, genetic and neuropathological studies. In recent years, diffusion tensor imaging (DTI) investigations have prompted interest in the key role of white matter (WM) abnormalities in BD. In this report, we summarize and comment recent findings from DTI studies in BD, reporting fractional anisotropy as putative measure of WM integrity, as well as recent data from neuropathological studies focusing on oligodendrocyte involvement in WM alterations in BD. DTI research indicates that BD is most commonly associated with a WM disruption within the fronto-limbic network, which may be accompanied by other WM changes spread throughout temporal and parietal regions. Neuropathological studies, mainly focused on the fronto-limbic network, have repeatedly shown a loss in cortical and subcortical oligodendrocyte cell count, although an increased subcortical oligodendrocyte density has been also documented suggesting a putative role in remyelination processes for oligodendrocytes in BD. According to our review, a greater integration between DTI and morphological findings is needed in order to elucidate processes affecting WM, either glial loss or myelin plasticity, on the basis of a more targeted research in BD.

The effect of ANK3 bipolar-risk polymorphisms on the working memory circuitry differs between loci and according to risk-status for bipolar disorder

Polymorphisms at the rs10994336 and rs9804190 loci of the Ankyrin 3 (ANK3) gene have been strongly associated with increased risk for bipolar disorder (BD). However, their potential pathogenetic effect on BD‐relevant neural circuits remains unknown. We examined the effect of BD‐risk polymorphisms at rs10994336 and rs9804190 on the working memory (WM) circuit using functional magnetic resonance imaging (fMRI) data obtained from euthymic patients with BD (n = 41), their psychiatrically healthy first‐degree relatives (n = 25) and unrelated individuals without personal or family history of psychiatric disorders (n = 46) while performing the N‐back task. In unrelated healthy individuals, the rs10994336‐risk‐allele was associated with reduced activation of the ventral visual cortical components of the WM circuit while the rs9804190‐risk‐allele was associated with inefficient hyperactivation of the prefrontal cortical components of the WM. In patients and their healthy relatives, risk alleles at either loci were associated with hyperactivation in the ventral anterior cingulate cortex. Additionally, Rs9804190‐risk‐allele carriers with BD evidenced abnormal hyperactivation within the posterior cingulate cortex. This study provides new insights on the neurogenetic correlates of allelic variation at different genome‐wide supported BD‐risk associated ANK3 loci that support their involvement in BD and highlight the modulatory influence of increased background genetic risk for BD.

The role of n-3 polyunsaturated fatty acids (n-3PUFAs) in affective disorders

BACKGROUND Among emerging treatments for depressive disorders several studies suggested that n-3 polyunsaturated fatty acids (n-3PUFAs) supplementation can be used. However, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) differ in terms of biochemistry, metabolism and therapeutic effects. Therefore, a clear picture of their specific and different role on affective disorders has not yet emerged. OBJECTIVES To investigate the effects of n-3PUFAs on affective disorders including major depression, bipolar disorder and perinatal depression. METHODS a comprehensive search on PUBMED, Medline and PsychINFO of all RCTs using n-3PUFAs patients with depressive symptoms published up to April 2016 was performed. We included trials that examined unipolar or bipolar disorder and trials that investigated depressive symptoms in relation to pregnancy. Trials were excluded if the depressive symptomatology was related to other primary organic diseases. RESULTS 264 RCT studies were identified but only 36 met the inclusion criteria. First, it has been reported that n-3PUFAs supplementation might have clinical benefits on depressive symptoms. Second, EPA supplement, rather than DHA, seems to be more effective in treating major depression. Third, n-3PUFAs can have beneficial effects in bipolar depression but not in perinatal depression. CONCLUSIONS there are only some evidence on the efficacy of n-3PUFAs in affective disorders especially to unipolar and bipolar depression not powered enough to confirm a therapeutic effect for affective disorder. Therefore, further studies with larger and more homogeneous samples, are required to confirm these effects.

The role of omega-3 fatty acids in developmental psychopathology: A systematic review on early psychosis, autism, and ADHD

In this systematic review, we will consider and debate studies that have explored the effects of ω-3 polyunsaturated fatty acids (PUFAs) in three major, and somehow related, developmental psychiatric disorders: Autism, Attention Deficit and Hyperactivity disorder and Psychosis. The impact of ω-3 PUFAs on clinical symptoms and, if possible, brain trajectory in children and adolescents suffering from these illnesses will be reviewed and discussed, considering the biological plausibility of the effects of omega-3 fatty acids, together with their potential perspectives in the field. Heterogeneity in study designs will be discussed in the light of differences in results and interpretation of studies carried out so far.

Metabolic alterations in generalised anxiety disorder: a review of proton magnetic resonance spectroscopic studies

Generalised anxiety disorder (GAD) is a common psychiatric illness characterised by selective morpho-functional brain alterations. The breath of neuroimaging studies investigating the neural basis of GAD is extensive; however, its pathophysiology is still largely unknown. Specifically for proton Magnetic Resonance Spectroscopy (¹H MRS) investigations, which have the aim of identifying differences in metabolite levels between conditions in key brain areas, often showed contrasting results. Indeed, there are selected ¹H MRS studies reporting deficits of key metabolites in GAD patients; however, collectively the literature remains mixed with respect to consistency of major findings. In this review, we evaluate published ¹H MRS studies on GAD with the final aim of providing a comprehensive overview of the extent of neurometabolic dysfunctions associated with GAD. Interestingly, the majority of the studies reviewed showed altered metabolite levels in the dorsolateral prefrontal cortex and hippocampus suggesting regional specificity. These results also provide evidence of the utility of ¹H MRS not only for elucidating the pathophysiology of neuropsychiatric diseases, but also for the identification of more beneficial and targeted pharmacological interventions. Additionally, future studies are warranted to overcome methodological differences observed across the studies.

Sexual dimorphism of the planum temporale in schizophrenia: A MRI study

Objective: Anatomical alterations in the superior temporal gyrus have been consistently reported in patients with schizophrenia, and they have mostly been linked to positive symptoms, including hallucinations and thought disorders. The superior temporal gyrus is considered one of the most asymmetric and lateralized structure of the human brain, and the process of lateralization seems to vary according to gender in the normal population. However, although it has been consistently suggested that patients with schizophrenia did not show normal brain lateralization in several regions, only few studies investigated it in the superior temporal gyrus and its sub-regions considering the effects of gender. In this context, the aim of this study was to evaluate sexual dimorphism in superior temporal gyrus volumes in a sample of patients with schizophrenia compared to age- and gender-matched healthy controls. Methods: A total of 72 right/left-handed males (40 schizophrenia patients and 32 healthy controls) and 45 right/left-handed females (18 schizophrenia patients and 27 healthy controls) underwent clinical evaluation and a 1.5T magnetic resonance imaging scan. Gray and white matter volumes of regions of interest within the superior temporal gyrus were manually detected, including the Heschl’s gyrus and the planum temporale. Results: Female patients with schizophrenia presented a reduction in left planum temporale gray matter volumes (F = 4.58, p = 0.03) and a lack of the normal planum temporale asymmetry index (t = 0.27; p = 0.79) compared to female controls (t = 5.47; p = 0.001). No differences were found between males for any volumes or laterality indices. Finally, in female patients with schizophrenia, Heschl’s gyrus gray and white matter volumes negatively correlated with positive symptoms (r = −0.56, p = 0.01). Conclusion: Our results showed that sexual dimorphism plays a key role on planum temporale in schizophrenia, underlining the importance of gender as a modulator of brain morphology and lateralization of schizophrenia.

Normative data and effects of age and gender on temperament and character dimensions across the lifespan in an Italian population: A cross-sectional validation study

BACKGROUND The short version of the Temperament and Character Inventory (TCI-125) has been employed for the study of personality traits in both clinical and normal populations. However, to the best of our knowledge, no studies explored the psychometric properties of this instrument in healthy individuals across the lifespan. We here provide the Italian normative data and present the personality features according to age and gender in a sample of healthy individuals. METHODS A cross-sectional study was carried out in a total of 1430 Italian healthy individuals ranging from 13 to 67 years (59.3% females). We evaluated the factorial model of the TCI-125, explored the internal consistency of the scales and carried out univariate analyses of variance for the investigation of age and gender differences in temperament and character dimensions. RESULTS Confirmatory factor analysis only partially confirmed the factor structure, with some Reward Dependence, Self-Directedness, and Cooperativeness items showing poor fit. Overall we found acceptable internal consistencies for all the dimensions of the TCI-125 across all age groups, except for Reward Dependence, Persistence, and Novelty Seeking, which showed unsatisfactory internal consistency in younger age groups. Furthermore, we found significant age differences in most temperament and all character dimensions. Finally, in specific age groups we also observed significantly lower scores in males compared to females in Harm Avoidance, Reward Dependence and all character dimensions except for Self-Directedness, on which males scored higher than females. CONCLUSIONS Although this study only partially confirmed the factor structure of the TCI-125 and suggested limited homogeneity for some temperament scales, overall our results supported the reliability of the TCI-125, which can therefore be considered a useful tool for exploring personality traits in both clinical and normal samples. Moreover, this study suggested the need of using this instrument with caution in adolescents.