Brain-based graph-theoretical predictive modeling to map the trajectory of anhedonia, impulsivity, and hypomania from the human functional connectome.

Clinical assessments often fail to discriminate between unipolar and bipolar depression and identify individuals who will develop future (hypo)manic episodes. To address this challenge, we developed a brain-based graph-theoretical predictive model (GPM) to prospectively map symptoms of anhedonia, impulsivity, and (hypo)mania. Individuals seeking treatment for mood disorders (n = 80) underwent an fMRI scan, including (i) resting-state and (ii) a reinforcement-learning (RL) task. Symptoms were assessed at baseline as well as at 3- and 6-month follow-ups. A whole-brain functional connectome was computed for each fMRI task, and the GPM was applied for symptom prediction using cross-validation. Prediction performance was evaluated by comparing the GPM to a corresponding null model. In addition, the GPM was compared to the connectome-based predictive modeling (CPM). Cross-sectionally, the GPM predicted anhedonia from the global efficiency (a graph theory metric that quantifies information transfer across the connectome) during the RL task, and impulsivity from the centrality (a metric that captures the importance of a region) of the left anterior cingulate cortex during resting-state. At 6-month follow-up, the GPM predicted (hypo)manic symptoms from the local efficiency of the left nucleus accumbens during the RL task and anhedonia from the centrality of the left caudate during resting-state. Notably, the GPM outperformed the CPM, and GPM derived from individuals with unipolar disorders predicted anhedonia and impulsivity symptoms for individuals with bipolar disorders. Importantly, the generalizability of cross-sectional models was demonstrated in an external validation sample. Taken together, across DSM mood diagnoses, efficiency and centrality of the reward circuit predicted symptoms of anhedonia, impulsivity, and (hypo)mania, cross-sectionally and prospectively. The GPM is an innovative modeling approach that may ultimately inform clinical prediction at the individual level.

SARS-CoV-2-associated first episode of acute mania with psychotic features.

Despite neuropsychiatric outcomes of SARS-CoV-2 infection are now under close scrutiny, psychoneuroimmunological characteristics of COVID-19 and precise pathophysiology of neuropsychiatric manifestations of the infection are still obscure. Moreover, there still exists a shortfall in demonstrating specific clinical manifestations of the brain involvement of the virus. Here, we presented a 33-year-old female patient with COVID-19, reporting acute-onset paranoid delusions symptoms, insomnia and irritability. Cranial MRI showed an hyperintense signal in the splenium of the corpus callosum with decreased apparent diffusion coefficient, which might possibly indicate the presence of cytotoxic edema related to the brain involvement of the infection. Following the completion of SARS-CoV-2 treatment, both cytotoxic edema and psychiatric symptoms resolved. In light of this report, we suggest that either heightened immune response and direct viral infection that SARS-CoV-2 may lead to such psychiatric manifestations and neuropsychiatric monitoring should be performed in patients with COVID-19. Prompt recognition of psychiatric consequences of COVID-19 may help clinicians provide guidance for differential diagnosis and manage them accordingly.

Altered dynamic functional connectivity across mood states in bipolar disorder.

BACKGROUND: This study aims to identify how the large-scale brain dynamic functional connectivity (dFC) differs between mood states in bipolar disorder (BD). The authors analyzed dFC in subjects with BD in depressed and euthymic states using resting-state functional magnetic resonance imaging (rsfMRI) data, and compared these states to healthy controls (HCs). METHOD: 20 subjects with BD in a depressive episode, 23 euthymic BD subjects, and 31 matched HCs underwent rsfMRI scans. Using an existing parcellation of the whole brain, we measured dFC between brain regions and identified the different patterns of brain network connections between groups. RESULTS: In the analysis of whole brain dFC, the connectivity between the left Superior Temporal Gyrus (STG) in the somatomotor network (SMN), the right Middle Temporal Gyrus (MTG) in the default mode network (DMN) and the bilateral Postcentral Gyrus (PoG) in the DMN of depressed BD was greater than that of euthymic BD, while there was no significant difference between euthymic BD and HCs in these brain regions. Euthymic BD patients had abnormalities in the frontal-striatal-thalamic (FST) circuit compared to HCs. CONCLUSIONS: Differences in dFC within and between DMN and SMN can be used to distinguish depressed and euthymic states in bipolar patients. The hyperconnectivity within and between DMN and SMN may be a state feature of depressed BD. The abnormal connectivity of the FST circuit can help identify euthymic BD from HCs.

A New Onset of Mania in a 49-Year-Old Man: An Interesting Case of Wilson Disease.

Wilson disease is a rare copper metabolism disorder that generally occurs in individuals between 5 and 35 years of age. Common clinical manifestations are hepatic, neurological, and psychiatric symptoms. Roughly, 4% of all cases occur in patients over 40 years of age and, among these patients, the presenting symptoms are generally neuropsychiatric, which often leads to misdiagnosis as a primary psychiatric disorder and a delay in correct diagnosis. This report presents the case of a 49-year-old man with no formal psychiatric history who presented with a new onset of mania. We outline the distinctive characteristics that appeared inconsistent with a primary psychiatric disorder and pointed toward secondary mania. Despite low serum ceruloplasmin, the absence of brain abnormalities more typical of Wilson disease on magnetic resonance imaging led a neurology consultant to advise that the diagnosis was likely primarily psychiatric. Due to atypical components of the patient's presentation, such as his late age of onset for bipolar disorder and acute cognitive decline, the psychiatric team advocated for further diagnostic workup. The subsequent evaluation confirmed Wilson disease based on specific ophthalmological and hepatic abnormalities and further copper studies. In addition, once diagnosed, the management of Wilson disease involves distinct clinical considerations given patients' presumed vulnerability to neurological side effects. This case illustrates the role psychiatric providers play in advocating for diagnostic workup in patients with atypical presentations of primary psychiatric disorders and the distinct diagnostic and treatment considerations associated with Wilson disease.

Mapping mania symptoms based on focal brain damage.

BACKGROUNDAlthough mania is characteristic of bipolar disorder, it can also occur following focal brain damage. Such cases may provide unique insight into brain regions responsible for mania symptoms and identify therapeutic targets.METHODSLesion locations associated with mania were identified using a systematic literature search (n = 41) and mapped onto a common brain atlas. The network of brain regions functionally connected to each lesion location was computed using normative human connectome data (resting-state functional MRI, n = 1000) and contrasted with those obtained from lesion locations not associated with mania (n = 79). Reproducibility was assessed using independent cohorts of mania lesions derived from clinical chart review (n = 15) and of control lesions (n = 490). Results were compared with brain stimulation sites previously reported to induce or relieve mania symptoms.RESULTSLesion locations associated with mania were heterogeneous and no single brain region was lesioned in all, or even most, cases. However, these lesion locations showed a unique pattern of functional connectivity to the right orbitofrontal cortex, right inferior temporal gyrus, and right frontal pole. This connectivity profile was reproducible across independent lesion cohorts and aligned with the effects of therapeutic brain stimulation on mania symptoms.CONCLUSIONBrain lesions associated with mania are characterized by a specific pattern of brain connectivity that lends insight into localization of mania symptoms and potential therapeutic targets.FUNDINGFundação para a Ciência e Tecnologia (FCT), Harvard Medical School DuPont-Warren Fellowship, Portuguese national funds from FCT and Fundo Europeu de Desenvolvimento Regional, Child Neurology Foundation Shields Research, Sidney R. Baer, Jr. Foundation, Nancy Lurie Marks Foundation, Mather's Foundation, and the NIH.

Opposing Changes in the Functional Architecture of Large-Scale Networks in Bipolar Mania and Depression.

OBJECTIVE: Manic and depressive phases of bipolar disorder (BD) show opposite symptoms in psychomotor, thought, and affective dimensions. Neuronally, these may depend on distinct patterns of alterations in the functional architecture of brain intrinsic activity. Therefore, the study aimed to characterize the spatial and temporal changes of resting-state activity in mania and depression, by investigating the regional homogeneity (ReHo) and degree of centrality (DC), in different frequency bands. METHODS: Using resting-state functional magnetic resonance imaging (fMRI), voxel-wise ReHo and DC were calculated-in the standard frequency band (SFB: 0.01-0.10 Hz), as well as in Slow5 (0.01-0.027 Hz) and Slow4 (0.027-0.073 Hz)-and compared between manic (n = 36), depressed (n = 43), euthymic (n = 29) patients, and healthy controls (n = 112). Finally, clinical correlations were investigated. RESULTS: Mania was mainly characterized by decreased ReHo and DC in Slow4 in the medial prefrontal cortex (as part of the default-mode network [DMN]), which in turn correlated with manic symptomatology. Conversely, depression was mainly characterized by decreased ReHo in SFB in the primary sensory-motor cortex (as part of the sensorimotor network [SMN]), which in turn correlated with depressive symptomatology. CONCLUSIONS: Our data show a functional reconfiguration of the spatiotemporal structure of intrinsic brain activity to occur in BD. Mania might be characterized by a predominance of sensorimotor over associative networks, possibly driven by a deficit of the DMN (reflecting in internal thought deficit). Conversely, depression might be characterized by a predominance of associative over sensorimotor networks, possibly driven by a deficit of the SMN (reflecting in psychomotor inhibition).