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      Neuropsychiatric Disease and Treatment (submit here)

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      Low hedonic tone and attention-deficit hyperactivity disorder: risk factors for treatment resistance in depressed adults

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          Abstract

          Background

          The burdens imposed by treatment-resistant depression (TRD) necessitate the identification of predictive factors that may improve patient treatment and outcomes. Because depression and attention-deficit hyperactivity disorder (ADHD) are frequently comorbid and share a complex relationship, we hypothesized that ADHD may be a predictive factor for the diagnosis of TRD. This exploratory study aimed to determine the percentage of undetected ADHD in those with TRD and evaluate factors associated with treatment resistance and undetected ADHD in depressed patients.

          Subjects and methods

          Adults referred (n=160) for psychiatric consultation completed a structured interview (MINI Plus, Mini International Neuropsychiatric Interview Plus) to assess the presence of psychiatric disorders.

          Results

          TRD was significantly associated with the number of diagnoses ( P<0.001), past ( P<0.001) and present medications ( P<0.001), chronic anhedonia ( P=0.013), and suicide ideation ( P=0.008). Undetected ADHD was present in 34% of TRD patients. The number of referral diagnoses ( P<0.001), failed medications ( P=0.002), and past selective serotonin reuptake inhibitor failures ( P=0.035) were predictive of undetected ADHD in TRD.

          Conclusion

          Undetected ADHD may be more prevalent among TRD patients than previously thought. In addition, TRD patients are more likely to present with psychiatric comorbidity than non-TRD patients. Screening patients with depression for the presence of ADHD and chronic anhedonia/low hedonic tone may help identify patients with TRD and undetected ADHD and improve treatment outcomes.

          Most cited references31

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          Architectonic subdivision of the human orbital and medial prefrontal cortex.

          The structure of the human orbital and medial prefrontal cortex (OMPFC) was investigated using five histological and immunohistochemical stains and was correlated with a previous analysis in macaque monkeys [Carmichael and Price (1994) J. Comp. Neurol. 346:366-402]. A cortical area was recognized if it was distinct with at least two stains and was found in similar locations in different brains. All of the areas recognized in the macaque OMPFC have counterparts in humans. Areas 11, 13, and 14 were subdivided into areas 11m, 11l, 13a, 13b, 13m, 13l, 14r, and 14c. Within area 10, the region corresponding to area 10m in monkeys was divided into 10m and 10r, and area 10o (orbital) was renamed area 10p (polar). Areas 47/12r, 47/12m, 47/12l, and 47/12s occupy the lateral orbital cortex, corresponding to monkey areas 12r, 12m, 12l, and 12o. The agranular insula (areas Iam, Iapm, Iai, and Ial) extends onto the caudal orbital surface and into the horizontal ramus of the lateral sulcus. The growth of the frontal pole in humans has pushed area 25 and area 32pl, which corresponds to the prelimbic area 32 in Brodmann's monkey brain map, caudal and ventral to the genu of the corpus callosum. Anterior cingulate areas 24a and 24b also extend ventral to the genu of the corpus callosum. Area 32ac, corresponding to the dorsal anterior cingulate area 32 in Brodmann's human brain map, is anterior and dorsal to the genu. The parallel organization of the OMPFC in monkeys and humans allows experimental data from monkeys to be applied to studies of the human cortex. Copyright 2003 Wiley-Liss, Inc.
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            The neural correlates of attention deficit hyperactivity disorder: an ALE meta-analysis.

            Attention deficit/hyperactivity disorder (ADHD) is one of the most prevalent and commonly studied forms of psychopathology in children and adolescents. Causal models of ADHD have long implicated dysfunction in fronto-striatal and frontal-parietal networks supporting executive function, a hypothesis that can now be examined systematically using functional neuroimaging. The present work provides an objective, unbiased statistically-based meta-analysis of published functional neuroimaging studies of ADHD. A recently developed voxel-wise quantitative meta-analytic technique known as activation likelihood estimation (ALE) was applied to 16 neuroimaging studies examining and contrasting patterns of neural activity in patients with ADHD and healthy controls. Voxel-wise results are reported using a statistical threshold of p < .05, corrected. Given the large number of studies examining response inhibition, additional meta-analyses focusing specifically on group differences in the neural correlates of inhibition were included. Across studies, significant patterns of frontal hypoactivity were detected in patients with ADHD, affecting anterior cingulate, dorsolateral prefrontal, and inferior prefrontal cortices, as well as related regions including basal ganglia, thalamus, and portions of parietal cortex. When focusing on studies of response inhibition alone, a more limited set of group differences were observed, including inferior prefrontal cortex, medial wall regions, and the precentral gyrus. In contrast, analyses focusing on studies of constructs other than response inhibition revealed a more extensive pattern of hypofunction in patients with ADHD than those of response inhibition. To date, the most consistent findings in the neuroimaging literature of ADHD are deficits in neural activity within fronto-striatal and fronto-parietal circuits. The distributed nature of these results fails to support models emphasizing dysfunction in any one frontal sub-region. While our findings are suggestive of the primacy of deficits in frontal-based neural circuitry underlying ADHD, we discuss potential biases in the literature that need to be addressed before such a conclusion can be fully embraced.
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              Ventral striatal hyporesponsiveness during reward anticipation in attention-deficit/hyperactivity disorder.

              Although abnormalities in reward processing have been proposed to underlie attention-deficit/hyperactivity disorder (ADHD), this link has not been tested explicitly with neural probes. This hypothesis was tested by using fMRI to compare neural activity within the striatum in individuals with ADHD and healthy controls during a reward-anticipation task that has been shown previously to produce reliable increases in ventral striatum activity in healthy adults and healthy adolescents. Eleven adolescents with ADHD (5 off medication and 6 medication-naïve) and 11 healthy controls (ages 12-17 y) were included. Groups were matched for age, gender, and intelligence quotient. We found reduced ventral striatal activation in adolescents with ADHD during reward anticipation, relative to healthy controls. Moreover, ventral striatal activation was negatively correlated with parent-rated hyperactive/impulsive symptoms across the entire sample. These findings provide neural evidence that symptoms of ADHD, and impulsivity or hyperactivity in particular, may involve diminished reward anticipation, in addition to commonly observed executive dysfunction.
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                Author and article information

                Journal
                Neuropsychiatr Dis Treat
                Neuropsychiatr Dis Treat
                Neuropsychiatric Disease and Treatment
                Neuropsychiatric Disease and Treatment
                Dove Medical Press
                1176-6328
                1178-2021
                2018
                17 September 2018
                : 14
                : 2379-2387
                Affiliations
                [1 ]START Clinic for Mood and Anxiety Disorders, Toronto, ON, Canada, mkatzman@ 123456startclinic.ca
                [2 ]Department of Psychology, Adler Graduate Professional School, Toronto, ON, Canada, mkatzman@ 123456startclinic.ca
                [3 ]Division of Clinical Sciences, The Northern Ontario School of Medicine, Thunder Bay, ON, Canada, mkatzman@ 123456startclinic.ca
                [4 ]Department of Psychology, Lakehead University, Thunder Bay, ON, Canada, mkatzman@ 123456startclinic.ca
                Author notes
                Correspondence: Martin A Katzman, START Clinic for Mood and Anxiety Disorders, 32 Park Road, Toronto, ON M4W 2N4, Canada, Tel +1 416 598 9344, Fax +1 416 598 8198, Email mkatzman@ 123456startclinic.ca
                Article
                ndt-14-2379
                10.2147/NDT.S170645
                6149933
                30271154
                f79461c3-78c9-45dd-a829-a7b453efc819
                © 2018 Sternat et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Neurology
                anhedonia,catecholamine,suicide,dopamine,attention,drug response
                Neurology
                anhedonia, catecholamine, suicide, dopamine, attention, drug response

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