array:24 [
  "pii" => "S2666275222000947"
  "issn" => "26662752"
  "doi" => "10.1016/j.abdp.2022.06.005"
  "estado" => "S300"
  "fechaPublicacion" => "2022-07-01"
  "aid" => "551"
  "copyright" => "Sociedade Brasileira de Dermatologia"
  "copyrightAnyo" => "2022"
  "documento" => "article"
  "crossmark" => 1
  "licencia" => "http://creativecommons.org/licenses/by/4.0/"
  "subdocumento" => "sco"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:1 [
    "total" => 0
  ]
  "Traduccion" => array:1 [
    "en" => array:19 [
      "pii" => "S036505962200071X"
      "issn" => "03650596"
      "doi" => "10.1016/j.abd.2021.02.011"
      "estado" => "S300"
      "fechaPublicacion" => "2022-07-01"
      "aid" => "551"
      "copyright" => "Sociedade Brasileira de Dermatologia"
      "documento" => "article"
      "crossmark" => 1
      "licencia" => "http://creativecommons.org/licenses/by/4.0/"
      "subdocumento" => "sco"
      "abierto" => array:3 [
        "ES" => true
        "ES2" => true
        "LATM" => true
      ]
      "gratuito" => true
      "lecturas" => array:1 [
        "total" => 0
      ]
      "en" => array:9 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Research Letter</span>"
        "titulo" => "The effects of isotretinoin on serotonin&#58; a prospective pilot study on acne patients"
        "tienePdf" => "en"
        "tieneTextoCompleto" => "en"
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "526"
            "paginaFinal" => "528"
          ]
        ]
        "contieneTextoCompleto" => array:1 [
          "en" => true
        ]
        "contienePdf" => array:1 [
          "en" => true
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Adam P&#46; Bray, Georgios Kravvas, Suzanne M&#46; Skevington, Christopher R&#46; Lovell"
            "autores" => array:4 [
              0 => array:2 [
                "nombre" => "Adam P&#46;"
                "apellidos" => "Bray"
              ]
              1 => array:2 [
                "nombre" => "Georgios"
                "apellidos" => "Kravvas"
              ]
              2 => array:2 [
                "nombre" => "Suzanne M&#46;"
                "apellidos" => "Skevington"
              ]
              3 => array:2 [
                "nombre" => "Christopher R&#46;"
                "apellidos" => "Lovell"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "en"
      "Traduccion" => array:1 [
        "pt" => array:9 [
          "pii" => "S2666275222000947"
          "doi" => "10.1016/j.abdp.2022.06.005"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => true
            "ES2" => true
            "LATM" => true
          ]
          "gratuito" => true
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "pt"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275222000947?idApp=UINPBA00008Z"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S036505962200071X?idApp=UINPBA00008Z"
      "url" => "/03650596/0000009700000004/v1_202206290808/S036505962200071X/v1_202206290808/en/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2666275222001023"
    "issn" => "26662752"
    "doi" => "10.1016/j.abdp.2022.06.013"
    "estado" => "S300"
    "fechaPublicacion" => "2022-07-01"
    "aid" => "563"
    "copyright" => "Sociedade Brasileira de Dermatologia"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by/4.0/"
    "subdocumento" => "sco"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "pt" => array:10 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Carta &#8208; Investiga&#231;&#227;o</span>"
      "titulo" => "O uso da internet para obten&#231;&#227;o de informa&#231;&#245;es dermatol&#243;gicas em pacientes da rede p&#250;blica&#58; estudo transversal"
      "tienePdf" => "pt"
      "tieneTextoCompleto" => "pt"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "528"
          "paginaFinal" => "531"
        ]
      ]
      "contieneTextoCompleto" => array:1 [
        "pt" => true
      ]
      "contienePdf" => array:1 [
        "pt" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0010"
          "etiqueta" => "Figura 2"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr2.jpeg"
              "Alto" => 1825
              "Ancho" => 2176
              "Tamanyo" => 128716
            ]
          ]
          "descripcion" => array:1 [
            "pt" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Padr&#245;es de associa&#231;&#227;o entre as fontes de busca&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Bianca Latance da Cruz, Arthur Cesar dos Santos Minato, Ioana Bittencourt Mour&#227;o, Dayane Neres Pereira, Miguel Huckembeck de Oliveira, Juliano Vilaverde Schmitt"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "Bianca Latance da"
              "apellidos" => "Cruz"
            ]
            1 => array:2 [
              "nombre" => "Arthur Cesar dos Santos"
              "apellidos" => "Minato"
            ]
            2 => array:2 [
              "nombre" => "Ioana Bittencourt"
              "apellidos" => "Mour&#227;o"
            ]
            3 => array:2 [
              "nombre" => "Dayane Neres"
              "apellidos" => "Pereira"
            ]
            4 => array:2 [
              "nombre" => "Miguel Huckembeck de"
              "apellidos" => "Oliveira"
            ]
            5 => array:2 [
              "nombre" => "Juliano Vilaverde"
              "apellidos" => "Schmitt"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "pt"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S0365059622000836"
        "doi" => "10.1016/j.abd.2020.12.015"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622000836?idApp=UINPBA00008Z"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275222001023?idApp=UINPBA00008Z"
    "url" => "/26662752/0000009700000004/v1_202207280537/S2666275222001023/v1_202207280537/pt/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S2666275222000881"
    "issn" => "26662752"
    "doi" => "10.1016/j.abdp.2022.05.011"
    "estado" => "S300"
    "fechaPublicacion" => "2022-07-01"
    "aid" => "553"
    "copyright" => "Sociedade Brasileira de Dermatologia"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by/4.0/"
    "subdocumento" => "sco"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "pt" => array:10 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Carta &#8208; Investiga&#231;&#227;o</span>"
      "titulo" => "Preval&#234;ncia de p&#234;nfigo na Col&#244;mbia de 2013 a 2017 segundo dados do Registro Nacional de Sa&#250;de"
      "tienePdf" => "pt"
      "tieneTextoCompleto" => "pt"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "523"
          "paginaFinal" => "526"
        ]
      ]
      "contieneTextoCompleto" => array:1 [
        "pt" => true
      ]
      "contienePdf" => array:1 [
        "pt" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Figura 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1386
              "Ancho" => 3062
              "Tamanyo" => 207207
            ]
          ]
          "descripcion" => array:1 [
            "pt" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Preval&#234;ncia de p&#234;nfigo vulgar&#44; p&#234;nfigo foli&#225;ceo e p&#234;nfigo foli&#225;ceo end&#234;mico &#40;fogo selvagem&#41; por faixa et&#225;ria na Col&#244;mbia entre 2013 e 2017&#46; &#42;Preval&#234;ncia por 100&#46;000 habitantes&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Daniel Fern&#225;ndez&#8208;Avila, Laura Charry&#8208;Anzola, Lina Gonz&#225;lez&#8208;Cardona"
          "autores" => array:3 [
            0 => array:2 [
              "nombre" => "Daniel"
              "apellidos" => "Fern&#225;ndez&#8208;Avila"
            ]
            1 => array:2 [
              "nombre" => "Laura"
              "apellidos" => "Charry&#8208;Anzola"
            ]
            2 => array:2 [
              "nombre" => "Lina"
              "apellidos" => "Gonz&#225;lez&#8208;Cardona"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "pt"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S0365059622000733"
        "doi" => "10.1016/j.abd.2021.01.005"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622000733?idApp=UINPBA00008Z"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275222000881?idApp=UINPBA00008Z"
    "url" => "/26662752/0000009700000004/v1_202207280537/S2666275222000881/v1_202207280537/pt/main.assets"
  ]
  "pt" => array:16 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Carta &#8208; Investiga&#231;&#227;o</span>"
    "titulo" => "Efeitos da isotretino&#237;na na serotonina&#58; estudo piloto prospectivo em pacientes com acne"
    "tieneTextoCompleto" => true
    "saludo" => "<span class="elsevierStyleItalic">Prezado Editor&#44;</span>"
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "526"
        "paginaFinal" => "528"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Adam P&#46; Bray, Georgios Kravvas, Suzanne M&#46; Skevington, Christopher R&#46; Lovell"
        "autores" => array:4 [
          0 => array:3 [
            "nombre" => "Adam P&#46;"
            "apellidos" => "Bray"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          1 => array:4 [
            "nombre" => "Georgios"
            "apellidos" => "Kravvas"
            "email" => array:1 [
              0 => "georgios.kravvas@nhs.net"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Suzanne M&#46;"
            "apellidos" => "Skevington"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Christopher R&#46;"
            "apellidos" => "Lovell"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:3 [
          0 => array:3 [
            "entidad" => "Bristol Dermatology Centre&#44; University Hospitals Bristol NHS Foundation Trust&#44; Bristol&#44; Reino Unido"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Manchester Centre for Health Psychology&#44; School of Psychological Sciences&#44; University of Manchester&#44; Manchester&#44; Reino Unido"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Kinghorn Dermatology Unit&#44; Royal United Hospital&#44; Bath&#44; Reino Unido"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Autor para correspond&#234;ncia&#46;"
          ]
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">A isotretino&#237;na &#40;&#225;cido 13&#8208;cis retin&#243;ico&#41; &#233; um tratamento altamente eficaz e comumente utilizado contra a acne vulgar&#46; Embora a isotretino&#237;na tenha sido associada a humor deprimido&#44; depress&#227;o e idea&#231;&#227;o suicida&#44; uma associa&#231;&#227;o concreta a mudan&#231;as adversas de humor ainda n&#227;o foi comprovada&#44; com alguns estudos apoiando essa afirma&#231;&#227;o e outros refutando&#8208;a&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#8211;6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Como a isotretino&#237;na atravessa a barreira hematoencef&#225;lica&#44; um mecanismo biol&#243;gico ligando a isotretino&#237;na &#224; depress&#227;o &#233; plaus&#237;vel&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3&#44;7&#8211;10</span></a> No c&#233;rebro adulto&#44; os receptores para retinoides s&#227;o amplamente expressos e a isotretino&#237;na pode potencialmente regular a express&#227;o de v&#225;rios genes neuronais&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#8211;10</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">A serotonina &#40;5&#8208;HT&#41; &#233; um neurotransmissor amplamente reconhecido e um mediador&#8208;chave do humor&#46; Desequil&#237;brios nos n&#237;veis de serotonina t&#234;m sido associados a humor deprimido e depress&#227;o&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7&#44;8</span></a> O objetivo deste estudo piloto foi testar a hip&#243;tese de que o tratamento com isotretino&#237;na pode levar a mudan&#231;as mensur&#225;veis nos n&#237;veis de neurotransmissores&#8208;chave relacionados ao humor&#46; Para isso&#44; foi realizado um estudo de coorte prospectivo para avaliar os efeitos da isotretino&#237;na sobre os neurotransmissores serotonina &#40;5&#8208;HT&#41; e 5&#8208;HIAA &#40;o principal metab&#243;lito da serotonina&#41; em pacientes com acne vulgar&#46; Os n&#237;veis plasm&#225;ticos de 5&#8208;HT e 5&#8208;HIAA foram medidos antes&#44; durante e ap&#243;s o tratamento com isotretino&#237;na&#46; Os dados foram coletados antes do in&#237;cio do tratamento&#44; aos dois e aos quatro meses de tratamento e um m&#234;s ap&#243;s o t&#233;rmino do tratamento&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Amostras de sangue de um total de 27 pacientes foram colhidas antes do in&#237;cio do tratamento&#46; Vinte e quatro e 22 pacientes foram submetidos a medidas no soro aos dois e aos quatro meses de tratamento&#44; respectivamente&#46; Apenas quatro pacientes compareceram para exames de sangue um m&#234;s ap&#243;s o t&#233;rmino do tratamento &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Na linha basal pr&#233;&#8208;tratamento&#44; foram encontrados os seguintes valores m&#233;dios&#58; 5&#8208;HT 10&#44;66 e 5&#8208;HIAA 74&#44;77&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Os valores m&#233;dios aos dois meses de tratamento foram&#58; 5&#8208;HT 9&#44;64 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;633&#41;&#44; 5&#8208;HIAA 44&#44;31 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;082&#41;&#46; Ap&#243;s quatro meses de terapia com isotretino&#237;na&#44; os valores foram&#58; 5&#8208;HT 13&#44;07 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;349&#41;&#44; 5&#8208;HIAA 32&#44;83 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;294&#41;&#46; Esses achados n&#227;o representaram mudan&#231;as estatisticamente significantes em rela&#231;&#227;o aos da linha basal&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">O n&#250;mero decepcionantemente baixo de pacientes que compareceram &#224; consulta de seguimento um m&#234;s ap&#243;s a interrup&#231;&#227;o do tratamento n&#227;o possibilitou uma an&#225;lise estat&#237;stica significativa dos efeitos p&#243;s&#8208;isotretino&#237;na&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Um registro detalhado dos achados ao longo do tempo&#44; bem como as rela&#231;&#245;es de mudan&#231;a de HT para HIAA&#44; s&#227;o fornecidas na <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">A rela&#231;&#227;o entre isotretino&#237;na e mudan&#231;as adversas de humor &#233; um aspecto altamente debatido da terapia com isotretino&#237;na&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">N&#227;o foi encontrada uma associa&#231;&#227;o significativa entre o tratamento com isotretino&#237;na e altera&#231;&#245;es nos neurotransmissores 5&#8208;HT&#44; 5&#8208;HIAA ou na rela&#231;&#227;o entre os dois&#46; Se houver uma liga&#231;&#227;o causal entre os dois&#44; &#233; prov&#225;vel que seja mediada por uma via neuroqu&#237;mica diferente&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Dito isso&#44; o presente estudo piloto tem um n&#250;mero pequeno de pacientes e uma perda significativa no seguimento&#46; Portanto&#44; mesmo que instrutivo&#44; o presente estudo n&#227;o pode apoiar totalmente essa afirma&#231;&#227;o&#46; Estudos maiores&#44; prospectivos e caso&#8208;controlados provavelmente ser&#227;o necess&#225;rios para abordar em detalhes a associa&#231;&#227;o entre humor&#44; isotretino&#237;na e neurotransmissores&#46; Espera&#8208;se que o presente estudo sirva de orienta&#231;&#227;o e inspira&#231;&#227;o para esses empreendimentos futuros&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Suporte financeiro</span><p id="par0060" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Contribui&#231;&#227;o dos autores</span><p id="par0065" class="elsevierStylePara elsevierViewall">Adam P&#46; Bray&#58; Contribuiu para a concep&#231;&#227;o&#44; recrutamento&#44; gest&#227;o&#44; reda&#231;&#227;o e revis&#227;o da literatura associada a este estudo&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Georgios Kravvas&#58; Contribuiu para a concep&#231;&#227;o&#44; recrutamento&#44; gest&#227;o&#44; reda&#231;&#227;o e revis&#227;o da literatura associada a este estudo&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Suzanne M&#46; Skevington&#58; Contribuiu para a concep&#231;&#227;o&#44; recrutamento&#44; gest&#227;o&#44; reda&#231;&#227;o e revis&#227;o da literatura associada a este estudo&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Christopher R&#46; Lovell&#58; Contribuiu para a concep&#231;&#227;o&#44; recrutamento&#44; gest&#227;o&#44; reda&#231;&#227;o e revis&#227;o da literatura associada a este estudo&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflito de interesses</span><p id="par0085" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:4 [
        0 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Suporte financeiro"
        ]
        1 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Contribui&#231;&#227;o dos autores"
        ]
        2 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Conflito de interesses"
        ]
        3 => array:1 [
          "titulo" => "Refer&#234;ncias"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2020-06-21"
    "fechaAceptado" => "2021-02-09"
    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Como citar este artigo&#58; Bray AP&#44; Kravvas G&#44; Skevington SM&#44; Lovell CR&#46; The effects of isotretinoin on serotonin&#58; a prospective pilot study on acne patients&#46; An Bras Dermatol&#46; 2022&#59;97&#58;526&#8211;8&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Trabalho realizado no Departamento de Dermatologia&#44; University Hospitals Bristol NHS Foundation Trust&#44; Bristol&#44; Reino Unido&#46;</p>"
      ]
    ]
    "multimedia" => array:2 [
      0 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Tabela 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Momentos no tempo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">5&#8208;HT &#38; 5&#8208;HIAA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Basal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 meses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 m&#234;s ap&#243;s o t&#233;rmino&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">N&#250;mero total de pacientes que contribuiu com dados em cada consulta</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Tabela 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Resultados dos testes ao longo do tempo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#250;mero de pacientes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">M&#237;n&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Quartil inferior&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mediana&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">M&#233;dia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Quartil superior&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">M&#225;x&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Testes de Wilcoxon n&#227;o param&#233;trico para compara&#231;&#227;o de duas amostras pareadas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#8208;HT&#95;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#44;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#44;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&#44;78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Comparador basal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#8208;HT&#95;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#44;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#44;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#44;64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#44;54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#44;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;633&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#8208;HT&#95;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#44;78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#44;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#44;77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&#44;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;349&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#8208;HIAA&#95;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#44;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#44;77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&#44;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">74&#44;77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">74&#44;86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">502&#44;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Comparador basal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#8208;HIAA&#95;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#44;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#44;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&#44;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#44;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">548&#44;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;082&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#8208;HIAA&#95;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#44;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#44;83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&#44;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">143&#44;70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;294&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HTHA&#95;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;098&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;249&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;605&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;527&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#44;220&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Comparador basal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HTHA&#95;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;203&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;312&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;475&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;496&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;803&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;523&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HTHA&#95;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;246&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;490&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;749&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;761&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;854&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;244&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Resumo n&#227;o param&#233;trico dos achados para 5&#8208;HT &#40;HT&#41;&#44; 5&#8208;HIAA &#40;HA&#41; e sua raz&#227;o &#40;HTHA&#41; na linha basal &#40;0&#41;&#44; ap&#243;s dois meses &#40;2&#41; e quatro meses &#40;4&#41; de tratamento</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Refer&#234;ncias"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:10 [
            0 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Isotretinoin and the Risk of Depression in Patients With Acne Vulgaris&#58; A Case&#8208;Crossover Study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "L&#46; Azoulay"
                            1 => "L&#46; Blais"
                            2 => "G&#46; Koren"
                            3 => "J&#46; Lelorier"
                            4 => "A&#46; Berard"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4088/jcp.v69n0403"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Psychiatry&#46;"
                        "fecha" => "2008"
                        "volumen" => "69"
                        "paginaInicial" => "526"
                        "paginaFinal" => "532"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18363422"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Is there an association between isotretinoin therapy and adverse mood changes&#63;&#46; A prospective study in a cohort of acne patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46;P&#46; Bray"
                            1 => "G&#46; Kravvas"
                            2 => "S&#46;M&#46; Skevington"
                            3 => "C&#46;R&#46; Lovell"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Dermatol Treat&#46;"
                        "fecha" => "2019"
                        "volumen" => "30"
                        "paginaInicial" => "796"
                        "paginaFinal" => "801"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Isotretinoin and psychopathology&#58; a review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "V&#46;P&#46; Kontaxakis"
                            1 => "D&#46; Skourides"
                            2 => "P&#46; Ferentinos"
                            3 => "B&#46;J&#46; Havaki-Kontaxaki"
                            4 => "G&#46;N&#46; Papadimitriou"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1744-859X-8-2"
                      "Revista" => array:5 [
                        "tituloSerie" => "Ann Gen Psychiatry"
                        "fecha" => "2009"
                        "volumen" => "8"
                        "paginaInicial" => "2"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19154613"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Association of suicide attempts with acne and treatment with isotretinoin&#58; retrospective Swedish cohort study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46; Sundstr&#246;m"
                            1 => "L&#46; Alfredsson"
                            2 => "G&#46; Sj&#246;lin-Forsberg"
                            3 => "B&#46; Gerd&#233;n"
                            4 => "U&#46; Bergman"
                            5 => "J&#46; Jokinen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/bmj.c5812"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMJ&#46;"
                        "fecha" => "2010"
                        "volumen" => "341"
                        "paginaInicial" => "c5812"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21071484"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Isotretinoin use and risk of depression&#44; psychotic symptoms&#44; suicide&#44; and attempted suicide"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46;S&#46; Jick"
                            1 => "H&#46;M&#46; Kremers"
                            2 => "C&#46; Vasilakis-Scaramozza"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/archderm.136.10.1231"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Dermatol&#46;"
                        "fecha" => "2000"
                        "volumen" => "136"
                        "paginaInicial" => "1231"
                        "paginaFinal" => "1236"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11030769"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The psychological and emotional impact of acne and the effect of treatment with isotretinoin"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "S&#46;C&#46; Kellett"
                            1 => "D&#46;J&#46; Gawkrodger"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1046/j.1365-2133.1999.02662.x"
                      "Revista" => array:7 [
                        "tituloSerie" => "Br J Dermatol&#46;"
                        "fecha" => "1999"
                        "volumen" => "140"
                        "paginaInicial" => "273"
                        "paginaFinal" => "282"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10233222"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0301211517301689"
                          "estado" => "S300"
                          "issn" => "03012115"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The neurobiology of retinoic acid in affective disorders"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;D&#46; Bremner"
                            1 => "P&#46; McCaffery"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.pnpbp.2007.07.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Prog Neuropsychopharmacol Biol Psychiatry&#46;"
                        "fecha" => "2008"
                        "volumen" => "32"
                        "paginaInicial" => "315"
                        "paginaFinal" => "331"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17707566"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Role of retinoid signaling in the adult brain"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46;A&#46; Lane"
                            1 => "S&#46;J&#46; Bailey"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.pneurobio.2005.03.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Prog Neurobiol&#46;"
                        "fecha" => "2005"
                        "volumen" => "75"
                        "paginaInicial" => "275"
                        "paginaFinal" => "293"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15882777"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Significance of vitamin A to brain function&#44; behavior and learning"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "C&#46;R&#46; Olson"
                            1 => "C&#46;V&#46; Mello"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/mnfr.200900246"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Nutr Food Res&#46;"
                        "fecha" => "2010"
                        "volumen" => "54"
                        "paginaInicial" => "489"
                        "paginaFinal" => "495"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20077419"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High expression of retinoic acid receptors and synthetic enzymes in the human hippocampus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "Y&#46;D&#46; Fragoso"
                            1 => "K&#46;D&#46; Shearer"
                            2 => "A&#46; Sementilli"
                            3 => "L&#46;V&#46; de Carvalho"
                            4 => "P&#46;J&#46; McCaffery"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00429-011-0359-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "Brain Struct Funct&#46;"
                        "fecha" => "2012"
                        "volumen" => "217"
                        "paginaInicial" => "473"
                        "paginaFinal" => "483"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22075950"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "pt"
  "url" => "/26662752/0000009700000004/v1_202207280537/S2666275222000947/v1_202207280537/pt/main.assets"
  "Apartado" => array:4 [
    "identificador" => "82068"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Carta - Investiga&#231;&#227;o"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/26662752/0000009700000004/v1_202207280537/S2666275222000947/v1_202207280537/pt/main.pdf?idApp=UINPBA00008Z&text.app=https://clinics.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275222000947?idApp=UINPBA00008Z"
]
Share
Journal Information
Vol. 97. Issue 4.
Pages 526-528 (1 July 2022)
Visits
6380
Vol. 97. Issue 4.
Pages 526-528 (1 July 2022)
Carta ‐ Investigação
Open Access
Efeitos da isotretinoína na serotonina: estudo piloto prospectivo em pacientes com acne
Visits
6380
Adam P. Braya, Georgios Kravvasa,
Corresponding author
georgios.kravvas@nhs.net

Autor para correspondência.
, Suzanne M. Skevingtonb, Christopher R. Lovellc
a Bristol Dermatology Centre, University Hospitals Bristol NHS Foundation Trust, Bristol, Reino Unido
b Manchester Centre for Health Psychology, School of Psychological Sciences, University of Manchester, Manchester, Reino Unido
c Kinghorn Dermatology Unit, Royal United Hospital, Bath, Reino Unido
This item has received

Under a Creative Commons license
Article information
Full Text
Bibliography
Download PDF
Statistics
Full Text
Prezado Editor,

A isotretinoína (ácido 13‐cis retinóico) é um tratamento altamente eficaz e comumente utilizado contra a acne vulgar. Embora a isotretinoína tenha sido associada a humor deprimido, depressão e ideação suicida, uma associação concreta a mudanças adversas de humor ainda não foi comprovada, com alguns estudos apoiando essa afirmação e outros refutando‐a.1–6

Como a isotretinoína atravessa a barreira hematoencefálica, um mecanismo biológico ligando a isotretinoína à depressão é plausível.3,7–10 No cérebro adulto, os receptores para retinoides são amplamente expressos e a isotretinoína pode potencialmente regular a expressão de vários genes neuronais.8–10

A serotonina (5‐HT) é um neurotransmissor amplamente reconhecido e um mediador‐chave do humor. Desequilíbrios nos níveis de serotonina têm sido associados a humor deprimido e depressão.7,8 O objetivo deste estudo piloto foi testar a hipótese de que o tratamento com isotretinoína pode levar a mudanças mensuráveis nos níveis de neurotransmissores‐chave relacionados ao humor. Para isso, foi realizado um estudo de coorte prospectivo para avaliar os efeitos da isotretinoína sobre os neurotransmissores serotonina (5‐HT) e 5‐HIAA (o principal metabólito da serotonina) em pacientes com acne vulgar. Os níveis plasmáticos de 5‐HT e 5‐HIAA foram medidos antes, durante e após o tratamento com isotretinoína. Os dados foram coletados antes do início do tratamento, aos dois e aos quatro meses de tratamento e um mês após o término do tratamento.

Amostras de sangue de um total de 27 pacientes foram colhidas antes do início do tratamento. Vinte e quatro e 22 pacientes foram submetidos a medidas no soro aos dois e aos quatro meses de tratamento, respectivamente. Apenas quatro pacientes compareceram para exames de sangue um mês após o término do tratamento (tabela 1).

Tabela 1.

Número total de pacientes que contribuiu com dados em cada consulta

Momentos no tempo  5‐HT & 5‐HIAA 
Basal  27 
2 meses  24 
4 meses  22 
1 mês após o término 

Na linha basal pré‐tratamento, foram encontrados os seguintes valores médios: 5‐HT 10,66 e 5‐HIAA 74,77.

Os valores médios aos dois meses de tratamento foram: 5‐HT 9,64 (p=0,633), 5‐HIAA 44,31 (p=0,082). Após quatro meses de terapia com isotretinoína, os valores foram: 5‐HT 13,07 (p=0,349), 5‐HIAA 32,83 (p=0,294). Esses achados não representaram mudanças estatisticamente significantes em relação aos da linha basal.

O número decepcionantemente baixo de pacientes que compareceram à consulta de seguimento um mês após a interrupção do tratamento não possibilitou uma análise estatística significativa dos efeitos pós‐isotretinoína.

Um registro detalhado dos achados ao longo do tempo, bem como as relações de mudança de HT para HIAA, são fornecidas na tabela 2.

Tabela 2.

Resumo não paramétrico dos achados para 5‐HT (HT), 5‐HIAA (HA) e sua razão (HTHA) na linha basal (0), após dois meses (2) e quatro meses (4) de tratamento

Resultados dos testes ao longo do tempo  Número de pacientes  Mín.  Quartil inferior  Mediana  Média  Quartil superior  Máx.  Testes de Wilcoxon não paramétrico para comparação de duas amostras pareadas 
5‐HT_0  27  0,61  4,59  8,70  10,66  13,04  36,78  Comparador basal 
5‐HT_2  24  1,26  5,89  7,60  9,64  11,54  28,32  p=0,633 
5‐HT_4  22  1,07  6,34  9,78  13,07  14,77  56,10  p=0,349 
5‐HIAA_0  26  7,05  14,77  26,23  74,77  74,86  502,30  Comparador basal 
5‐HIAA_2  24  3,11  13,19  23,05  44,31  29,03  548,20  p=0,082 
5‐HIAA_4  22  2,26  8,50  25,67  32,83  41,12  143,70  p=0,294 
HTHA_0  26  0,012  0,098  0,249  0,605  0,527  5,220  Comparador basal 
HTHA_2  21  0,015  0,203  0,312  0,475  0,496  1,803  p=0,523 
HTHA_4  20  0,015  0,246  0,490  0,749  0,761  2,854  p=0,244 

A relação entre isotretinoína e mudanças adversas de humor é um aspecto altamente debatido da terapia com isotretinoína.

Não foi encontrada uma associação significativa entre o tratamento com isotretinoína e alterações nos neurotransmissores 5‐HT, 5‐HIAA ou na relação entre os dois. Se houver uma ligação causal entre os dois, é provável que seja mediada por uma via neuroquímica diferente.

Dito isso, o presente estudo piloto tem um número pequeno de pacientes e uma perda significativa no seguimento. Portanto, mesmo que instrutivo, o presente estudo não pode apoiar totalmente essa afirmação. Estudos maiores, prospectivos e caso‐controlados provavelmente serão necessários para abordar em detalhes a associação entre humor, isotretinoína e neurotransmissores. Espera‐se que o presente estudo sirva de orientação e inspiração para esses empreendimentos futuros.

Suporte financeiro

Nenhum.

Contribuição dos autores

Adam P. Bray: Contribuiu para a concepção, recrutamento, gestão, redação e revisão da literatura associada a este estudo.

Georgios Kravvas: Contribuiu para a concepção, recrutamento, gestão, redação e revisão da literatura associada a este estudo.

Suzanne M. Skevington: Contribuiu para a concepção, recrutamento, gestão, redação e revisão da literatura associada a este estudo.

Christopher R. Lovell: Contribuiu para a concepção, recrutamento, gestão, redação e revisão da literatura associada a este estudo.

Conflito de interesses

Nenhum.

Referências
[1]
L. Azoulay, L. Blais, G. Koren, J. Lelorier, A. Berard.
Isotretinoin and the Risk of Depression in Patients With Acne Vulgaris: A Case‐Crossover Study.
J Clin Psychiatry., 69 (2008), pp. 526-532
[2]
A.P. Bray, G. Kravvas, S.M. Skevington, C.R. Lovell.
Is there an association between isotretinoin therapy and adverse mood changes?. A prospective study in a cohort of acne patients.
J Dermatol Treat., 30 (2019), pp. 796-801
[3]
V.P. Kontaxakis, D. Skourides, P. Ferentinos, B.J. Havaki-Kontaxaki, G.N. Papadimitriou.
Isotretinoin and psychopathology: a review.
Ann Gen Psychiatry, 8 (2009), pp. 2
[4]
A. Sundström, L. Alfredsson, G. Sjölin-Forsberg, B. Gerdén, U. Bergman, J. Jokinen.
Association of suicide attempts with acne and treatment with isotretinoin: retrospective Swedish cohort study.
BMJ., 341 (2010), pp. c5812
[5]
S.S. Jick, H.M. Kremers, C. Vasilakis-Scaramozza.
Isotretinoin use and risk of depression, psychotic symptoms, suicide, and attempted suicide.
Arch Dermatol., 136 (2000), pp. 1231-1236
[6]
S.C. Kellett, D.J. Gawkrodger.
The psychological and emotional impact of acne and the effect of treatment with isotretinoin.
Br J Dermatol., 140 (1999), pp. 273-282
[7]
J.D. Bremner, P. McCaffery.
The neurobiology of retinoic acid in affective disorders.
Prog Neuropsychopharmacol Biol Psychiatry., 32 (2008), pp. 315-331
[8]
M.A. Lane, S.J. Bailey.
Role of retinoid signaling in the adult brain.
Prog Neurobiol., 75 (2005), pp. 275-293
[9]
C.R. Olson, C.V. Mello.
Significance of vitamin A to brain function, behavior and learning.
Mol Nutr Food Res., 54 (2010), pp. 489-495
[10]
Y.D. Fragoso, K.D. Shearer, A. Sementilli, L.V. de Carvalho, P.J. McCaffery.
High expression of retinoic acid receptors and synthetic enzymes in the human hippocampus.
Brain Struct Funct., 217 (2012), pp. 473-483

Como citar este artigo: Bray AP, Kravvas G, Skevington SM, Lovell CR. The effects of isotretinoin on serotonin: a prospective pilot study on acne patients. An Bras Dermatol. 2022;97:526–8.

Trabalho realizado no Departamento de Dermatologia, University Hospitals Bristol NHS Foundation Trust, Bristol, Reino Unido.

Copyright © 2022. Sociedade Brasileira de Dermatologia
Download PDF
Idiomas
Anais Brasileiros de Dermatologia
Article options
Tools
en pt
Cookies policy Política de cookies
To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here. Utilizamos cookies próprios e de terceiros para melhorar nossos serviços e mostrar publicidade relacionada às suas preferências, analisando seus hábitos de navegação. Se continuar a navegar, consideramos que aceita o seu uso. Você pode alterar a configuração ou obter mais informações aqui.